Stem cell treatments are redefining the essence of classical medicine for a variety of conditions.
TISSU is an ethical organisation which was formed in conjunction with the Government of Seychelles to remedy the many problems seen with the numerous small, illegal stem cell clinics currently in operation around the world. Unlike other clinics all our results from all treatments will be published in peer reviewed medical journals
The Seychelles Government has fully authorised the use of stem cell treatments in its country, which will undoubtedly eventually become legalised throughout the rest of the Western world, as stem cell research continues to astound us with life changing new developments.
Stem cell research has great promise for the treatment of a variety of diseases, and stem cell therapy holds exciting prospects for continuing medical advances in the next few decades. The scientific, legal, ethical and philosophical arguments have been discussed extensively and each day we read about the emergence of these new discoveries.
Tissu operates completely legally under the auspices of the Seychelles Government and National Hospital; all the stem cells and treatment protocols are available and results are all reported in peer reviewed reputable medical journals. Our objective is to help you with stem cell treatment if you need it.
Our philosophy is that we will only treat conditions with stem cells for which there is evidence and benefit, unlike other clinics that will treat anyone provided they can pay the fees. Some of our treatments are free or considerably subsidised for those who cannot afford the full payment.
Tissu aims to provide a stem cell treatment that is a smooth, stress free journey towards treating your condition. Every detail will be taken care of, allowing you to channel all your mental energy towards recovery. Prior to treatment you will receive a certified analysis of the stem cells that will be used to treat your condition.
Tissu Stem Cell clinics provide stem cell treatments for degenerative diseases and anti-ageing treatments, using stem cells only under strictly prescribed conditions. The stem cells are carefully counted and we use around twenty million stem cells per treatment; this is why our treatments have better results compared to other clinics that use only a few thousand poor quality cells. Throughout the entire process quality and sterility is maintained from manufacture through to transport and final administration to the patient.
Treatment is delivered only by medical practitioners who are guided by the strictest of protocols and in keeping with worldwide best practice, ensuring an uncompromising level of quality care that has become the benchmark in stem cell treatment. The new hospital in the Seychelles, which will complete construction in March 2009, will be where most of the treatments will be based. Tissu also has a clinic based in the clinic suites at Eden Island. All transfers on the island are arranged by Tissu with no cost to the patient.
Our expert scientific team have already created many of the benchmarks for stem cell treatment (for example, all patients receive an MRI prior to treatment to assess the benefit of treatments), which many other clinics already aspire to follow. These protocols are used to administer the stem cells and associated growth factors to each patient.
Most patients will receive the cells into the blood system as an intravenous infusion; stem cell implantation or treatment to patients with stem cells can occur into the peripheral blood through an intravenous cannula, whilst for some cardiac conditions it is into the arterial system using an arterial catheter or, in neurological conditions, into the fluid surrounding the spinal cord via a lumbar puncture.
All treatments will be performed as outpatient treatments in the Tissu Clinic, with all of the treatments taking place in the clinic’s day procedure unit. This is a sterile environment for treatments, much like many Western hospital day-stay units. Some patients may need the use of diagnostic imaging procedures such as CT for the placement of cells; these patients will be treated either at the Seychelles Victoria Hospital or the new International Hospital.
No allergic reactions have ever been documented. Stem cells are immunologically “immature”, lacking the ability to be recognized by the immune system, making the risk of an immune reaction very unlikely.
Nevertheless, in order to ensure that you do not have any problems, all patients undergoing treatment are observed and monitored daily for 2 - 3 days at the clinic.
The stem cells are as safe as many blood products from a blood bank, as they are tested twice, before and after processing, to make sure they are free from disease and contamination before being cryopreserved. Testing is for a myriad of bacterial and viral infections including HIV, Hepatitis B and bovine spongiform-encephalitis (mad-cow disease).
Although relatively new to the scene of cell based therapies for reparative medicine, stem cells and their progenitors have been labelled as the ‘cell of the future’ for revolutionising the treatment of spinal cord injury, CNS injury and neurodegenerative disorders. Another stem cell source that is being pursued, and that may in fact be closer to the goal of producing a variety of spinal cord cells, is stem cells from the spinal cord itself. These are a subclass of neural stem cells and as such are restricted to generating neural tissues.
Bone marrow precursor stem cells or mononuclear cellular fractions of bone marrow contain mesenchymal stem cells and haematopoetic stem cells. These stem cells are a component of bone marrow that preferentially migrate to the site of brain injury and differentiate into neurons and cell supporting elements, improving functional outcome in animals.
Many studies have indicated that transplantation of several different types of stem cells promotes functional recovery in animal models of spinal cord injury. These studies have been confirmed by anecdotal reports of miraculous recovery in some patients with spinal cord injuries.
One approach to using stem cells for regenerative therapies may be recruitment of endogenous neural stem cells resident in the adult spinal cord. Researchers have showed that stem cell-derived motor nerve cells, when grafted, sent projections to reach muscle targets, and stem cell grafts improved motor function in animal models with acute and chronic spinal cord injury.
In some studies stem cells have promoted functional recovery in animals with spinal cord injury. These animals showed an improvement in locomotor (movement) rating scales and also showed somatosensory-evoked potentials (sensation) recovery.
Studies in humans have also shown that subarachnoid placement of stem cells is safe with no long term adverse effects. Some of the reports of treatment are truly amazing.
Three kinds of stem/progenitor cells have been used in cell therapy in animal models of spinal cord injury: embryonic stem cells, bone marrow mesenchymal stem cells, and umbilical cord neural stem cells. Neural stem cells or fate-restricted neuronal or glial progenitor cells were preferably used because they have the clear capacity to become neurons or glial cells after transplantation into the injured spinal cord.
At least a part of the functional deficits after spinal cord injury is attributable to chronic progressive demyelination. Therefore, several studies transplanted glial-restricted progenitors or oligodendrocyte precursors to target the demyelination process. Transplanted stem/progenitor cells can also contribute to promoting axonal regeneration by functioning as cellular scaffolds for growing axons, such as occurs with other stem cell treatments in multiple sclerosis.
Spinal cord injury has been recognized as one of the conditions for which stem cell transplantation may first prove beneficial. After spinal cord injury loss of localized myelinating oligodendrocytes and grey matter neurons occurs, with glial scar formation and degeneration of both descending and ascending axons. Replacement of oligodendrocytes to promote remyelination, or of neurons to assuage neuronal loss and damage through establishment of relay circuitry or release of trophic factors, are possibilities for stem cell treatments.
Currently there are no published clinical trials in humans that have been performed, mainly because the clinics giving these treatments do not have legal approval in their home country. The Seychelles has given legal approval for stem cell treatment and all results are available and documented in clinical trials and published in peer reviewed journals.
Most spinal cord injury causes permanent disability or loss of movement (paralysis) and sensation below the site of the injury. Paralysis that involves the majority of the body, including the arms and legs, is called quadriplegia or tetraplegia. When a spinal cord injury affects only the lower body, the condition is called paraplegia.
Spinal cord injury symptoms depend on two factors:
A complete spinal cord injury is defined by total or near-total loss of motor function and sensation below the area of injury. However, even in a complete injury, the spinal cord is almost never completely cut in half. Doctors use the term “complete” to describe a large amount of damage to the spinal cord. It’s a key distinction because many people with partial spinal cord injuries are able to experience significant recovery, while those with complete injuries are not.
In 1995, actor Christopher Reeve had a horse riding accident and severely damaged his spinal cord, leaving him paralyzed from the neck down. From then until his death in 2004, the Superman movie actor became the most famous face of spinal cord injury.
Fifty years ago, a spinal cord injury was usually fatal. At that time, most injuries were severe, complete injuries and little treatment was available.
Today, there is still no way to reverse damage to the spinal cord. But modern injuries are usually less severe, partial spinal cord injuries and advances in recent years have improved the recovery of people with a spinal cord injury, and significantly reduced the amount of time survivors must spend in hospital. Researchers are working on new treatments, including innovative treatments, prostheses and medications that may promote nerve cell regeneration or improve the function of the nerves that remain after a spinal cord injury. The most dramatic results are being achieved with stem cell treatments.
In the meantime, spinal cord injury treatment focuses on preventing further injury and enabling people with a spinal cord injury to return to an active and productive life within the limits of their disability. This requires ongoing care and rehabilitation.
After the initial injury or disease stabilizes, doctors turn their attention to problems that may arise from immobilization, such as de-conditioning, muscle contractures, bedsores, urinary infection and blood clots. Early care will likely include range-of-motion exercises for paralyzed limbs, help with bladder and bowel functions, applications of skin lotion, and use of soft bed coverings or flotation mattresses, as well as frequently changing the patient’s position.
It’s often impossible for a doctor to make a precise prognosis right away. Recovery, if it occurs, typically starts between a week and six months after injury. Impairment remaining after 12 to 24 months is likely to be permanent.
However, some people experience small improvements for up to two years or longer. At one point, Christopher Reeve made national headlines when he regained the ability to move his fingers and wrists and feel sensations more than five years after he was paralyzed in a horse riding accident. But many not-so-famous people with a spinal cord injury have made similar strides away from the media spotlight. Doctors are researching ways to improve and perhaps augment this late recovery with the use of stem cell treatments.
Often the cord is not completely severed during injury; even so, swelling cuts off the blood supply to the neurons and glial cells. Without a blood supply these cells die. Additional cell death occurs as cells from the immune system migrate to the injury site. In order for a connection to be re-established new neurons and glial cells must regenerate to replace the injured ones. Up until about ten years ago people believed that there was no possibility for neurogenesis of adult nerve cells. Once nerve cells were damaged they were gone, eliminating hope for complete recovery from paralysis. As a result, treatments for spinal cord injury focused on prevention of further damage (secondary damage) and rehabilitation.
While the majority of cells found in the central nervous system are born during the embryonic and early postnatal period, scientists recently discovered that new neurons are continuously added to two specific regions of the adult mammalian brain (Reynolds and Weiss 1992). Animal studies have shown that neural stem cells were isolated from the dentate gyrus of the hippocampus and the walls of the ventricular system called the ependymal layer. These pluripotent stem cells divide and the daughter cells differentiate into other neuronal cells. These stem cells also migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into neurons and glial cells (Luskin, 1993). Nerve cell differentiation has been witnessed in vivo, as well as in vitro when stimulated with an epidermal growth factor (Gage, 1995).
The discovery of differentiating stem cells in the brain revolutionized the way scientists think about treating spinal cord injury. Suddenly the chance for partial or possibly full recovery from paralysis seemed like a plausible option. Attention shifted to regenerating the neurons and glial cells as a solution to spinal cord injury.
Along with pluripotent stem cells, progenitor cells, a more restricted type of stem cells, are found in the hippocampus and ependymal layer. These stem cells are immature cells that are predetermined to differentiate into neurons, oligodendrocytes, and astrocytes. In 1995 Frissen observed that the presence of nestin increases in response to spinal cord injury. Nestin is a protein expressed by stem cells: presence of it indicates neural stem cells are much more active then previously believed. Our brain naturally increases the production of stem cells to aid an injured CNS. If the brain responds in this way, why doesn’t the spinal cord repair itself?
In 1999, Johansson and Momma observed that only active progenitor cells were differentiating into astrocytes. They labeled ependymal cells with a Dil injection so migration could be followed. After making lesions in the spinal cord they waited four weeks and then observed the progress of the ependymal cells. They tested the cells found in the scar tissue around the site of injury and found that all DIL marked cells were astrocytes. This indicates that the progeny from ependymal cells had only differentiated to astrocytes. Stem cells do respond to spinal cord injury, just not for the purpose of re-establishing connection between neurons. Thus by utilising other neural stem cells to aid this process of re-establishing connection the treatment of spinal cord injury would be easily achieved.
Enzmann, GU; Benton, RL; Talbott, JF; Cao, Q; Whittemore, SR. Functional considerations of stem cell transplantation therapy for spinal cord repair. J Neurotrauma. 2006;23:479–495
Wrathall JR, Lytle JM. Stem cells in spinal cord injury. Dis Markers. 2008;24(4-5):239-50. ReviewSafety of Autologous Stem Cell Treatment for Traumatic Brain Injury in Children Charles S. Cox, Jr., M.D. The University of Texas Health Science Center, Houston
Stem cell delivery by lumbar puncture as a therapeutic alternative to direct injection into injured spinal cord. J Neurosurg Spine. 2008 Oct;9(4):390-9. Neuhuber B, Barshinger AL, Paul C, Shumsky JS, Mitsui T, Fischer I
Stem cell therapy and coordination dynamics therapy to improve spinal cord injury. Electromyogr Clin Neurophysiol. 2008 Jun-Jul;48(5):233-53. Schalow G.
Neurally induced umbilical cord blood cells modestly repair injured spinal cords. Neuroreport. 2008 Aug 27;19(13):1259-63. Cho SR, Yang MS, Yim SH, Park JH, Lee JE, Eom YW, Jang IK, Kim HE, Park JS, Kim HO, Lee BH, Park CI, Kim YJ.
Stem cell transplantation in India: tall claims, questionable ethics. Indian J Med Ethics. 2008 Jan-Mar;5(1):15-7. Pandya SK.
Stem Cell. 2008 Jul 3;3(1):16-24. Stem cells for spinal cord repair.Barnabé-Heider F, Frisén J.
Stem cells in spinal cord injury Dis Markers. 2008;24(4-5):239-50. Wrathall JR, Lytle JM.
Stem cell-based cell therapy for spinal cord injury. Cell Transplant. 2007;16(4):355-64Kim BG, Hwang DH, Lee SI, Kim EJ, Kim SU..
Neuronal repair and replacement in spinal cord injury. J Neurol Sci. 2008 Feb 15;265(1-2):63-72Bareyre FM.
Stem cells for the treatment of spinal cord injury. Exp Neurol. 2008 Feb;209(2):368-77. Coutts M, Keirstead HS.
Setting the stage for functional repair of spinal cord injuries: a cast of thousands. Spinal Cord. 2005 Mar;43(3):134-61. Ramer LM, Ramer MS, Steeves JD.
Neurological aspects of spinal-cord repair: promises and challenges. Lancet Neurol. 2006 Aug;5(8):688-94. Dietz V, Curt A
Stem and progenitor cell therapies: recent progress for spinal cord injury repair. Neurol Res. 2008 Feb;30(1):5-16Louro J, Pearse DD.
Integration and translation: driving stem cell therapies toward the clinic. Regen Med. 2008 May;3(3):269-73. Trounson A.
Recent research has revealed that neural stem cells are present in normal adult brain, and have the potential to compensate and recover neural functions that were lost due to ischaemic stroke. Endogenous neural stem cells have been identified in the central nervous system where they reside largely in the subventricular zone and in the subgranular zone of the hippocampus. These endogenous stem cells, which have been shown to reside throughout life in the central nervous system, have the capacity to replace lost neurons in models for numerous disorders, including cerebral ischaemia.
Progress has been made in isolating human adult neural stem cells and demonstrating the feasibility of autologous neural stem cell transplantation. An increasing number of studies provide evidence that haematopoietic stem cells, either after stimulation of endogenous stem cell pools or after exogenous haematopoietic stem cell application (transplantation), improve functional outcome after ischaemic brain lesions. Various underlying mechanisms such as transdifferentiation into neural lineages, neuroprotection through trophic support, and cell fusion have been postulated and remain areas of active research.
Further studies to discover homing mechanisms of stem cells will be important in the context of developing strategies to enhance the therapeutic benefits of stem cells following systemic administration. Research activities focusing on stem cells, which represent a promising source for neural cell replacement and functional recovery after stroke, have gained momentum in recent years, making regenerative cell-based therapies a much more feasible realistic approach. This is the approach that Tissu employs in treating patients, who have had strokes previously and have still not fully recovered.
Current evidence shows in large case series that functional recovery from stroke reaches a maximum level by 3-6 months after onset, and no further recovery occurs beyond this time. Nevertheless, about 80% of these patients reach their maximum function for activities of daily living within 6 weeks from onset. Accordingly, in subjects with first-ever ischaemic stroke who remained neurologically unchanged from the second until the third month after the acute event, implementation of stem cell therapy would be appropriate at approximately 3 months after the stroke.
Several hypotheses to account for these therapeutic benefits of stem cell in treating strokes have been suggested, including neuroprotective effects from release or stimulation of growth factors and cytokines, the induction of neovascularization, and the replacement of damaged cells by these stem cells.
Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Recent studies demonstrate that systemic administration of human cord blood-derived CD34(+) cells to immunocompromised mice subjected to stroke 48 hours earlier, induces new vessel growth (neovascularisation) in the ischaemic zone and provides a favourable environment for neuronal regeneration.
Endogenous nerve growth is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. This data suggests an essential role for CD34(+) cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed leading to speedier recovery without disability.
We are currently researching into the expeditious treatment of strokes with stem cells to see if full recovery can occur quicker.
An increasing number of studies and preclinical trials have provided evidence that regenerative stem cell-based therapies can lead to functional recovery in stroke patients. Stem cells can differentiate into neural lineages to replace lost neurons. Moreover, they provide growth support to tissue at risk in the penumbra surrounding the infarct area, enhance new vessel formation and help promote survival, migration, and differentiation of the endogenous precursor cells after stroke. Stem cells are highly migratory and seem to be attracted to areas of brain pathology such as ischemic regions. They may follow the paradigm of stem cell homing to bone marrow and leukocytes migrating to inflammatory tissue being drawn to these areas by cytokines.
Animal studies show that stem cells improve functional deficit without reduction of infarct volume and with very rare differentiation of the stem cell. These experimental studies suggest that stem cells would support cerebral plasticity (cerebral tissue’s ability to regenerate) via growth factor production and stimulation of endogenous mechanisms of local repair. Assessment of effectiveness in the use of stem cells in cerebral ischaemia still requires further investigation as outlined above.
The ultimate repair for the brain should restore the entire lost structure and it’s function. However, partial benefit is possible from addressing some of the needs of the injured brain. These partial solutions are the basis of current research into brain repair after stroke. An opportunity arises for two kinds of intervention: (1) replacement of neurons; (2) support of existing neurons, to prevent excessive degeneration and promote rewiring and plasticity.
The future of brain repair and regeneration following stroke with stem cells is likely to require some form of combination therapy (perhaps with several stem cell types) designed to replace the lost neural cells and supporting structure, attract new blood supply, support and enhance intrinsic repair and plasticity mechanisms.
Stroke or cerebrovascular accident is a life threatening event, on account of the brain being starved of oxygen. It is the third commonest cause of death in the UK and the leading cause of severe disability and the commonest cause of disability in the Western world.
Recurrent stroke is frequent; about 25 percent of people who recover from their first stroke will have another stroke within 5 years.
There are two main types of stroke:
Although stroke is a disease of the brain, it can affect the entire body. A common disability that results from stroke is complete paralysis on one side of the body, called hemiplegia. A related disability that is not as debilitating as paralysis is one-sided weakness or hemiparesis. Stroke may cause problems with thinking, awareness, attention, learning, judgment, and memory. Stroke survivors often have problems understanding or forming speech. A stroke can lead to emotional problems. Stroke patients may have difficulty controlling their emotions or may express inappropriate emotions. Many stroke patients experience depression. Stroke survivors may also have numbness or strange sensations.
Generally there are three treatment stages for stroke: prevention, therapy immediately after the stroke, and post-stroke rehabilitation. Therapies to prevent a first or recurrent stroke are based on treating an individual’s underlying risk factors for stroke, such as hypertension, atrial fibrillation, and diabetes. At the present time, ischaemic stroke can be treated at the acute phase by thrombolysis with a recombinant of the tissue-plasminogen activator, which must be administered within the first 3 hours.
Acute cerebral infarction causes irreversible locally restricted loss of the neuronal circuitry and supporting glial cells with consecutive functional deficits and disabilities. The currently available and effective therapy targets fast vessel re-canalisation (re-opening). Acute stroke therapies try to stop a stroke while it is happening by quickly dissolving the blood clot causing an ischemic stroke.
Post-stroke rehabilitation helps individuals overcome disabilities that result from stroke damage. Medication or drug therapy is the most common treatment for stroke. The most popular classes of drugs used to prevent or treat stroke are antithrombotics (antiplatelet agents and anticoagulants) and thrombolytics. At present, thrombolytic therapy inducing re-canalization (re-opening) of the occluded vessels in the cerebral infarcted area is a commonly used therapeutic strategy. However, only a minority of patients have timely access to this kind of therapy. Therefore, finding other techniques to effectively treat stroke patients is vitally important.
The treatments options available for improvement of neurological function after stroke is currently limited to placement in specialized stroke units, optimal therapy for medical complications, and intense physical, occupational and speech rehabilitation. Despite many trials, no pharmacological intervention has been shown convincingly to improve neurological outcome. Thus if newer treatment modalities such as stem cell treatment offers improved neurological function or restoration of neurological function they would revolutionise treatments.
Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia Experimental Neurology, Volume 199, Issue 1, May 2006, Pages 56-66T. Honma, O. Honmou, S. Iihoshi, K. Harada, K. Houkin, H. Hamada and J.D. Kocsis
Optimization of a therapeutic protocol for intravenous injection of human mesenchymal stem cells after cerebral ischemia
Yoshinori Omoria, Osamu Honmoua, Kuniaki Haradaa, Junpei Suzukia,Kiyohiro Houkina, Jeffery D. Kocsisc
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8543, Japan
Experimental neurology 2006, vol. 199, no 1 pp. 37-41Time course and outcome of recovery from stroke: Relevance to stem cell treatment GILMAN Department of Neurology, University of Michigan
Current Clinical Neurology Vascular Dementia Cerebrovascular Mechanisms and Clinical Management 10.1385/1-59259-824-2:331 Robert H. Paul, Ronald Cohen, Brian R. Ott and Stephen Salloway Marc Fisher6 and Magdy Selim
Stem cell sources and therapeutic approaches for central nervous system and neural retinal disorders Journal of Neurosurgery March 2008 vol 24 no 3-4 Diana Yu, B.S.1, and Gabriel A. Silva, Ph.D.Departments of Bioengineering and 2Ophthalmology, and 3Neurosciences Program, University of California, San Diego, California
Curr Opin Neurol (2005) 18: 59-64. Adult stem cell therapy in stroke. S Haas, N Weidner, J Winkler
Journal of Cerebral Blood Flow & Metabolism (2000) 20, 1393–1408; Therapeutic Potential of Neurotrophic Factors and Neural Stem Cells Against Ischemic Brain Injury Koji Abe
Leker RR Manipulation of endogenous neural stem cells following ischemic brain injury Pathophysiol Haemost Thromb 2006;35 (1-2):58-62 Department of Neurology, Peritz Scheinberg Cerebrovascular Research Laboratory and the Agnes Ginges Center for Human Neurogenetics.
From bench to bedside: should we believe in the efficacy of stem cells in cerebral ischaemia? Morphologie. 2005 Sep;89(286):154-67 Tran-Dinh A, Kubis N. Centre de Recherche Cardiovasculaire, INSERM U689, Hôpital Lariboisière, Paris.
Stroke research priorities for the next decade - a representative view of the European scientific community. Cerebrovasc Dis. 2007;23(4):318-9; Meairs S, Wahlgren N, Dirnagl U, Lindvall O, Rothwell P, Baron JC, Hossmann K, Engelhardt B, Ferro J, McCulloch J, Kaste M, Endres M, Koistinaho J, Planas A, Vivien D, Dijkhuizen R, Czlonkowska A, Hagen A, Evans A, De Libero G, Nagy Z, Rastenyte D, Reess J, Davalos A, Lenzi GL, Amarenco P, Hennerici M
Fadini GP, Agostini C, Avogaro A. Endothelial progenitor cells in cerebrovascular disease. Stroke. 2005 Jan;36(1):151-3.
Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004 Aug;114(3):330-8 Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T Department of Cerebrovascular Disease, National Cardiovascular Center, Osaka, Japan.
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Department of Neurosurgery, University of Illinois at Chicago, Chicago, IL, USA.
Regenerative therapy for stroke. Chang YC Shyu WC Lin SZ Li H Cell Transplant 2007; 16 (2) ; 171-81
Anti aging medicine or regenerative medicine is an extension of preventive health care, and is the next great model of health care for the new millennium.
This form of medicine is focused on the very early detection, prevention, and reversal of age-related disease. This includes heart disease, most cancers, adult-onset diabetes, stroke, high blood pressure, osteoporosis, arthritis, osteoarthritis, autoimmune disease, glaucoma, and Alzheimer’s. With early detection and appropriate intervention, most of these diseases can be prevented, cured, or have their downward course reversed. If we could slow ageing we could eliminate almost 50% of all adult diseases
Stem cell therapy as a therapeutic intervention against ageing is derived from the use of stem cells for over 30 years. Utilising the benefits of research into stem cells and clinical application stem cell therapies have been successfully utilized around the world to treat a wide range of aging-related disorders, including heart disease, diabetes, stroke, cancer, arthritis, Parkinson’s disease, and other neurodegenerative diseases and diseases associated with ageing metabolism.
As we age, our stem cell reserves with which we are born, decline. Our cells diminish in their ability to regenerate and repair tissue. Age-related changes occur in the skin, organs, sex glands, immune system, blood-forming system, muscles and other systems. These changes are all due to the decrease in the function and loss of stem cells. As our body’s cells become progressively weaker over time and perish, their replacement with new stem cells can slow down ageing. Evidence of an “anti-aging” effect of stem cells is reported in medical literature. In one report, fetal liver stem cell and cord blood stem cell preparations improved immune function and hormonal balance in patients undergoing cosmetic procedures, and thereby enhanced the cosmetic outcome.
Stem cell anti-ageing therapy is the replacement of diseased, dysfunctional, aged or injured cells with either stem cells or activation of the body’s own latent stem cells. This is somewhat similar to the organ transplant process but uses stem cells instead of organs. Perhaps this is why the process of ageing can be slowed down with the supplementation of stem cells. Stem cell therapy or stem cell transplantation is often referred to as regenerative medicine. This field of regenerative medicine is at the forefront of advances in anti-ageing therapies.
Stem cells are different from other types of cells in two ways:
In the 70’s the use of vitamins was introduced, the 80’s brought herbal remedies from the Eastern world to the West. In the 90’s, anti-oxidants and exotic juices came into the marketplace. Nowadays we have stem cell treatments. But until now, no marketed substance has yet been proven to slow or reverse human aging. Finally, after years of research, science has discovered the natural renewal system of our bodies. By being able to assist our bodies to achieve optimal health we will allow ourselves to live a long fruitful life.
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As we age, three major concerns seem to be at the top of our list: freedom from disease, an alert brain, and physical function. Remarkably, stem cells seem to be able to improve all three.
Through regenerative medicine and anti-ageing treatments we can enjoy life and well being to our full potential for longer. No longer will age be the impediment to our quality of life.
Scientists used to believe that our cells did not begin to degenerate (ageing-process) until about the age of 36, but research has found that cell degeneration begins in the womb and continuing shortly after birth.
Cells are constantly turned over or replaced and replenished e.g. skin and hair cells are continuously growing from an adult’s own supply of stem cells. Unfortunately this source is quite small and obviously depletes over time. The best example of the constant replenishment of cells from stem cells is the blood, which is made of red blood cells that are continuously replaced from haematopoietic stem cells as they only survive for 120 days.
As we grow older, the ability of the repair mechanisms in our bodies lessen, allowing free-radical damage to accumulate; cells, tissues, and organs become impaired, and we become more vulnerable to disease. The result, wrinkles, stiff joints, loss of muscle and bone mass, reduced hearing and our ability to heal diminish. We bruise easier as our skin becomes thinner and is less elastic. Imagine how we would feel today if we could have started the anti-aging process in our thirties.
Stem cells repair, regenerate and rejuvenate the diseased organ, thus limiting the further progress of the disease itself, as well as halting the ageing process; your immune response may also be enhanced thereby further slowing down the disease process or ageing. Treatment with stem cell therapy is not a cure, it is a process of repair, regeneration and rejuvenation that occurs at varying levels. This is why stem cell treatment is so effective and essential for anti ageing.
Stem cell treatment itself also modulates the immune mechanism as stem cells themselves act as mild immunosuppressive agents. This may allow the body’s own healing and regenerative capacity to become more effective.
Research has revealed that bone marrow stem cells constitute the natural renewal system of the body. Simply supporting the release of stem cells from the bone marrow allows the body to combat ageing naturally thereby promoting optimal health. Over the past ten years or so, profound advancements have been made in the area of stem cell research and anti-aging, so much so that almost all anti ageing therapies now include a stem cell component.
The question posed is that if we can repair ourselves then why do we need stem cell treatments? One theory is that there are not enough stored stem cells to constantly repair the body’s tissues as they are recruited for more vital tasks such as replacing red blood cells. Stem cell treatment is the replacement of diseased, dysfunctional, aged or injured cells with mesenchymal stem cells.resulting in the benefits of anti ageing, i.e. a more enjoyable and healthier life.
Researchers have shown for the first time that putting two specific types of neural cells directly into an aging brain can kick-start creation of brain cells linked to learning and memory. (1)
Cardiomyocytes that die in response to disease processes or aging are replaced by scar tissue instead of new muscle cells. Although recent reports suggest an intrinsic capacity for the mammalian myocardium to regenerate via endogenous stem cells, the magnitude of such a response appears to be limited, although beneficial, but has yet to be realized fully in patients with heart disease. If this process can be augmented via stem cell treatments then survival rates following heart disease will increase.
Studies from multiple laboratories have shown that transplantation of donor cells (e.g. fetal cardiomyocytes, skeletal myoblasts, smooth muscle cells, and adult stem cells) can improve the function of diseased hearts over a short period of time (1 - 4 weeks). While long-term follow-up studies are warranted, it is generally perceived that the beneficial effects of transplanted cells are mainly due to increased angiogenesis or scar remodeling in the engrafted myocardium.
“The level of CD34+ (stem cells) is one of the best predictors of cardiovascular health. The higher number of circulating stem cells, the greater the cardiovascular health”….. “The level of stem cells in the blood was a better predictor of heart attack than cholesterol level”. New England Journal of Medicine Sept. 8, 2005.
This is a major finding and provides a foundation for the suggestion that stem cells contribute to the ongoing repairs needed for a healthy heart and overall health. Enhancing the number of stem cells in the blood seems to be a very important factor for maintaining cardiovascular health.
Mesenchymal stem cell treatment is promising as a cell-based therapeutic strategy for cardiovascular disease. The possible therapeutic role of mesenchymal stem cells in vascular stenosis has been investigated. Researchers have tested the effectiveness of allogenic bone marrow-derived mesenchymal stem cells in reduction of stenosis in research studies. They have shown that the internal size of the arteries is larger with stem cell treatment and there will be less regrowth of stenotic lesion. Stem cells also lowered the levels of inflammation-related genes after arteriotomy. (2)
Skin is an organ whose function is far beyond a physical barrier between the inside and the outside of the body. Skin is composed of the epidermis, dermis and matrix. The dermis is a tissue rich in matrix elements and poor in cellular content. It is accepted that modifications occurring in the matrix are those which mostly contribute to skin ageing, by altering its biomechanical properties. Therefore it is common to address questions related to skin ageing by considering alterations in matrix molecules like collagen.
Researchers have undertaken investigations in stem cells related to fibroblasts, which are the cells responsible for the formation and maintenance of the dermis. It has now been shown that these fibroblasts from stem cells in classical culture on plastic exhibit very different morphologies associated with different secretion properties, allowing the reproduction of a three-dimensional architecture resembling skin in vivo (within the human body).
Scientists are now generating preparations that contain fibroblasts from stem cells that grow and form your own natural collagen and skin. This collagen matrix assumes the same structure as normal young healthy skin and so reduces the visible appearance of wrinkling.
In healthy individuals, skin integrity is maintained by epidermal stem cells, which self-renew and generate daughter cells that undergo terminal differentiation. Despite accumulation of senescence markers in aged skin, epidermal stem cells are maintained at normal levels throughout life. Therefore, skin ageing is induced by impaired stem cell mobilisation or a reduced number of stem cells able to respond to proliferative signals from damaged skin. In the skin, the existence of several distinct stem cell populations has been reported.
Genetic labelling studies have detected multipotent stem cells of the hair follicle bulge to support regeneration of hair follicles, but is not responsible for maintaining interfollicular epidermis, which exhibits a distinct stem cell population. Hair follicle epithelial stem cells have at least a dual function: hair follicle remodelling in daily life and epidermal regeneration whenever skin integrity is severely compromised, e.g. after burns.
Bulge cells (or stem cells of the hair follicle), the first adult stem cells of the hair follicle have been identified. These are capable of forming hair follicles, interfollicular epidermis and sebaceous glands. In addition, they can also give rise to non-epithelial cells, indicating a lineage-independent pluripotent character. Multipotent stem cells (skin-derived precursor cells) are present in human dermis; dermal stem cells represent 0.3% among human dermal fibroblasts.
A resident pool of stem cells exists within the sebaceous gland, which is able to differentiate into both sebocytes and interfollicular epidermis. The self-renewal and multi-lineage differentiation of skin stem cells make these cells attractive for treatment of the ageing process but also for regenerative medicine, tissue repair, gene therapy and cell-based therapy with autologous adult stem cells, not only in dermatology. In addition, they provide in vitro models to study epidermal lineage selection and its role in the ageing process.
Adipose-derived stem cells (ADSCs) and their secretory factors can stimulate collagen synthesis and migration of fibroblasts during the wound healing process. This is currently utilised in many stem cell treatments for burns, for example stem cell impregnated burns dressings. Conventional treatments for skin aging, such as lasers and topical regimens, induce new collagen synthesis via activation of dermalstem cell fibroblasts or growth factors. Therefore ADSCs can also be used for the treatment of skin ageing.
Researchers have analyzed secretory factors of ADSCs and intradermally injected ADSCs (1 x 10(6) cells in 1 mL of Hanks’ buffered salt solution) and conditioned media of ADSCs on the skin. In addition, as a pilot study, intradermal injections of purified autologous processed lipoaspirate (PLA) cells were tried with the photoaged skin of one patient. The results demonstrated that ADSCs produce many useful growth factors, increase collagen production in animal study, and reverse skin aging in human trial. These scientists concluded that stem cell treatment for skin via their secretory factors showed promise for application in cosmetic dermatology, especially in the treatment of skin aging.
No studies have yet been done specifically to answer this question but we do know that the quality of stem cells diminishes with ageing. Some answers can be drawn from medical experience with chemotherapy and radiation therapy. Before undergoing such therapy, which kills all stem cells in the body, doctors harvest stem cells from the patients. These stem cells are later injected in the patient to repopulate the bone marrow. Before harvesting stem cells, patients are injected with compounds known to stimulate stem cell release from the bone marrow. It has been observed that older people release fewer stem cells than younger people. This seems to be a clear correlation with age.
Whether this comes from the reduced ability to make stem cells or to release them is not well documented but recent studies suggest that as we age the number of stem cells also declines. However, we know that the bone marrow slowly turns from red marrow (stem cell producing) to yellow marrow or fatty marrow (which does not produce stem cells) as we age. This may explain why fewer stem cells are released as we grow older.
Data suggests that antioxidants help cell function. Grape seed extract is at its best when combined with the bioflavonoids in bilberry and cranberry. Other berry and tomato based anti-oxidants are also needed. Another anti-oxidant, Pomegranate extracts, should contain punicalagin for optimum antioxidant activity. Other antioxidants are vitamin C, green tea, bilberry and grape seed.
All vitamins and minerals play a role in maintaining the good health of stem cells, as well as other cells throughout the body.
Melatonin has been shown to support the proliferation of neural stem cells. Melatonin is produced during sleep and suppressed by prolonged exposure to screens (televisions, computers etc). So, good sleep should help the body and brain recover faster and better.
So far, no food has been studied for its effect on stem cells. There is enough data to suggest that antioxidant and anti-inflammatory food could help overall stem cell physiology and slow ageing.
Various studies have collectively shown that the higher the number of stem cells in the blood, the greater overall health, thus fighting the anti-aging process. This was specifically shown in cardiovascular health in a paper published in the New England Journal of Medicine. There are different hypotheses as to the actual effect on health. More stem cells may simply mean more stem cells for migration, and hence a greater potential to repair. So rather than the body deteriorating as we grow older we now have an opportunity to repair much of the damage from ageing that has been done. There is a big difference between living a long life and living a long healthy life.
1. http://www.dukehealth.org/HealthLibrary/News/10088
2. Adipose-Derived Stem Cells and Their Secretory Factors as a Promising Therapy for Skin Aging.Park BS, Jang KA, Sung JH, Park JS, Kwon YH, Kim KJ, Kim WS. J Dermatol Surg. 2008 Jun 27.
3. Anti-aging diagnosis and therapy: fact and fiction Zech NH Gynakol Geburtshilfliche Rundsch. 2004 Apr;44(2):113-22. Review. German. Mesenchymal stem cells effectively reduce surgically induced stenosis in carotids. Forte A, Finicelli M, Mattia M, Berrino L, Rossi F, De Feo M, Cotrufo M, Cipollaro M, Cascino A, Galderisi U. J Cell Physiol. 2008 Dec;217(3):789-99.
4. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57:B333-B338 (2002)
5. © 2002 The Gerontological Society of America
6. Is There an Antiaging Medicine? Robert N. Butlera, Michael Fosselb, S. Mitchell Harmanc, Christopher B. Hewardc, S. Jay Olshanskyd, Thomas T. Perlse, David J. Rothmanf, Sheila M. Rothmang, Huber R. Warnerh, Michael D. Westi and Woodring E. Wright
7. The regenerative potential of stem cell therapeutics in the anti-aging setting.
8. Publication: Townsend Letter for Doctors and Patients Publication Date: 01-DEC-05 Goldman, Robert ; Klatz, Ronald
Adult stem cell therapy has shown great promise at regenerating the central nervous system in general. In Parkinson’s disease in particular, the dopamine producing neurons that die are responsible for connecting a structure in the brain called the substantia nigra to another structure called the striatum, which is composed of the caudate nucleus and the putamen. Such “nigro-striatal” neuronal connections allow for the release and transfer of the chemical transmitter dopamine onto their target neurons in the striatum, which controls body movement. These dopamine producing neurons can be replaced with stem cell transplantation.
As previously described, it is the degeneration of these dopamine producing neurons which results in Parkinson’s disease. Logically, therefore, it is the regeneration of these same dopamine producing neurons which restores normal body movement and reverses the symptoms of Parkinson’s disease. Adult stem cells have been shown to be effective at this regeneration, with the neuronal connections re-established well into the striatum.
Cell transplantation therapies have been used to treat certain neurodegenerative diseases such as Parkinson’s and Huntington’s disease. However, ethical concerns over the use of fetal tissues (embryonic stem cells), and the inherent complexities of standardising the procurement, processing and transplantation methods of this tissue, have prompted the search for a source of cells that have less ethical stigmatisations, are readily available and can be easily standardised. Several sources of human cells that meet these principles have been under investigation.
Stem cells from human umbilical cord blood are one source that is consistent with these principles; therefore, they have become of great interest in the field of cellular repair / replacement for the treatment of CNS diseases, neurodegenerative diseases and injury. Furthermore, umbilical cord stem cells are easily available and less immunogenic compared to other sources for stem cell therapy such as bone marrow.
It is neither necessary nor advisable to use embryonic stem cells in such a therapy, since adult stem cells carry the required pluripotency to differentiate into neurological tissue; adult stem cells lack the risk of forming teratomas (tumors) which have always been the identifying feature of embryonic stem cells. Ethics and politics aside, purely from a scientific perspective, the characteristics and behaviour of adult stem cells are highly preferable to those of embryonic stem cells.
The ability of umbilical cord blood stem cells to treat these neurodegenerative diseases may be attributed to the inherent ability of stem cell populations to replace damaged tissues. Alternatively, various cell types within the graft may promote neural repair by delivering neural protection and secretion of neurotrophic factors.
Even within the brain itself, the white matter is known to contain multipotent progenitor cells that are able to differentiate into all the major cell types of the brain, including neurons. Scientists are therefore hoping to discover additional ways in which to stimulate the brain’s own stem cells for localised repair and regeneration.
Specific stem cells have been discovered in two locations within the adult primate brain, namely, in the subventricular zone and in the dentate gyrus of the hippocampus. In the 1990s, researchers discovered that stem cells from these two areas of the brain are naturally mobilized and stimulated automatically to migrate toward a site of injury, whenever the brain incurs damage.
Stem cell transplantation / replacement has emerged as the novel therapeutic strategy for Parkinson’s disease. Stem cells offer the potential to provide a virtually unlimited supply of optimized dopamine producing neurons that can provide enhanced benefits. Stem cell treatments have now been shown to be capable of differentiating into dopamine neurons that provide benefits following transplantation in animal models of Parkinson’s disease.
There have been numerous advances in enhancing the yield of dopamine producing neurons from stem cells, and promoting their survival and consequent clinical effects. As Parkinson’s disease involves degeneration of both dopaminergic (dopamine producing) and non-dopaminergic neurons, it also remains to be determined if transplantation of even the ideal dopamine producing neuron will improve non-dopaminergic features of the disease or provide benefits superior to existing therapies.
Clinical trials with transplanting dopamine producing tissue have provided evidence that stem cell transplantation could be a viable alternative to current traditional treatments.
The stem cell transplantation in the animal model of Parkinson’s disease proves that it is capable of relieving symptoms and restoring damaged brain function. Future stem cell research should focus not only on ameliorating the symptoms of Parkinson’s disease but also on neuroprotection or neurorescue that can favorably modify the natural course and slow the progression of the disease. Some of these cells have been the subject of clinical trials, which to date have produced variable outcomes. Therefore, whilst cell therapies remain a promising treatment for Parkinson’s disease, there is need for further refinement of the techniques involved in this procedure.
Parkinson’s disease belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine producing brain cells. The four primary symptoms of Parkinson’s disease are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. Parkinson’s disease usually affects people over the age of 50.
Early symptoms of Parkinson’s disease are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of Parkinson’s disease patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes, difficulty in swallowing, chewing, and speaking, urinary problems or constipation, skin problems and sleep disruptions.
There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic Parkinson’s disease. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases.
At present, there is no cure for Parkinson’s disease, but a variety of medications provide dramatic relief from the symptoms. Usually, patients are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain’s dwindling supply. Although levodopa helps at least three-quarters of Parkinson’s disease cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced. Problems with balance and other symptoms may not be alleviated at all. Anticholinergics may help control tremor and rigidity.
Other drugs, such as bromocriptine, pramipexole, and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms. In May 2006, the FDA approved rasagiline to be used along with levodopa for patients with advanced Parkinson’s disease or as a single-drug treatment for early Parkinson’s disease.
In some cases, surgery may be appropriate if the disease doesn’t respond to drugs. A therapy called deep brain stimulation (DBS) has now been approved by the U.S. Food and Drug Administration. In DBS, electrodes are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS can reduce the need for levodopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of levodopa. It also helps to alleviate fluctuations of symptoms and to reduce tremors, slowness of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work correctly.
Parkinson’s disease is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. Although some people become severely disabled, others experience only minor motor disruptions. Tremor is the major symptom for some patients, while for others tremor is only a minor complaint and other symptoms are more troublesome. No one can predict which symptoms will affect an individual patient, and the intensity of the symptoms also varies from person to person.
The National Institute of Neurological Disorders and Stroke (NINDS) conducts Parkinson’s disease research in laboratories at the National Institutes of Health (NIH) and also supports additional research through grants to major medical institutions. Current research programs funded by the NINDS are using animal models to study how the disease progresses and to develop new drug therapies. Scientists looking for the cause of Parkinson’s disease continue to search for possible environmental factors, such as toxins, that may trigger the disorder, and study genetic factors to determine how defective genes play a role. Other scientists are working to develop new protective drugs that can delay, prevent, or reverse the disease.
Curr Opin Neurol. 2005 Aug;18(4):376-85. Stem cell treatment for Parkinson’s disease: an update for 2005. Snyder BJ, Olanow CW.
Neural stem cells for Parkinson’s disease: To protect and repair
Paul R. Sanberg* Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine,
Newman MB Davis CD Borlongan CV Emerich D Sanberg PR Transplantation of Human umbilical cord blood cells in the repair of CNS diseases. Expert Opin Biol Ther. 2004 Feb;4(2):121-30 from the Center of Excellence for ageing and brain repair University of South Florida college of medicine Tampa FL USA
Curr Opin Neuorl 2005 Aug;18(4): 376-85 Stem cell treatment for Parkinson’s disease: an update for 2005 Snyder BL Olanow CW
Curr Neurovasc Res 2007 May;4(2):99-109 Current advances in the treatment of Parkinsons disease with stem cells. Trzaska KA Rameshwar P
J Neuroimmune Pharmacol 2007 Sep;2 (3):243-50 Stem cell transplantation: a promising therapy for Parkinson’s disease. Wang Y Chen S Yang D Le WD.
Neurodegener Dis 2007;4(4): 339-47 Stem cell based strategies for the treatment of Parkinsons disease Parish CL Arenas E
J Neurol Sci 2008 Feb 15;265(1-2): 32-42 Laguna Goya R Tyers P Barker RA The search for a curative cell therapy in Parkinson’s disease
Although effective immunotherapies exist which down-regulate the autoimmune anti-myelin reactivity and reduce the rate of relapses of multiple sclerosis (like Copaxone and interferons), there is no effective means today to stop the progression of disability and induce rebuilding of the destroyed myelin (re-myelination).
There is currently no permanent cure for multiple sclerosis, although there are several treatments available for ameliorating the symptoms and managing the neurological conditions as a result of the disease process.
Medical treatments currently are aimed at returning function after an attack and preventing disability rather than tackling the pathophysiological disease process.
Neuronal stem cells have been shown to possess the ability to restore neuronal activity and produce new neurons through transdifferentiation. Various other types of stem cells have been tested in animal models with promising results, revealing a potential for restoration of the neurological function in neuroimmune and neurodegenerative conditions and in central nervous system traumatic injury.
Adult bone marrow derived mesenchymal stromal cells (MSC) have been shown to induce similar (to the neuronal stem cells) immunomodulatory and neuroregenerative effects and were shown in our laboratory to induce neuroprotection in the animal model of chronic experimental autoimmune encephalomyelitis (EAE).
These bone marrow derived mesenchymal stromal cells offer practical advantages for clinical therapeutic applications, since they can be obtained from the adult bone marrow and therefore the patient can be the donor for himself, without any danger for rejection of the cells. In addition, mesenchymal stromal cells carry a safer profile and are less prone to malignant transformation.
Future medical therapies need to effect mechanisms that will aid the remyelinating of chronically demyelinated axons. Two distinct approaches should be evaluated in order to promote myelin repair; firstly the endogenous myelin repair processes may be stimulated through the delivery of growth factors, and secondly the repair process could be augmented through the delivery of exogenous stem cells with potential for myelination and regeneration.
Effective treatment for multiple sclerosis also requires modulation of the immune system, since demyelination is associated with specific immunological activation and chronic auto immune inflammatory response.
Karussis and Kassis described how different stem cells migrated to areas within white matter lesions (plaques) and possess the ability to support the regrowth of neurons and regeneration of the affected myelin. This is postulated to occur through both the endogenous resident CNS stem cells regenerating and by differentiation of the transplanted stem cells into neurons and myelin-producing oligodendrocytes. These stem cells also possess immunomodulating properties which are crucial if treatment for multiple sclerosis is to halt the auto immune inflammatory process.
Several types of stem cells have the capacity for promoting myelin repair, as well as modulating the immune response; stem cells are therefore potential candidates for the successful treatment of multiple sclerosis. With inflammatory diseases which are diffuse and widespread such as multiple sclerosis, intravenous injection of stem cells can be used and has been demonstrated as an appropriate means of diffuse delivery of stem cells.
Many different stem cell types, including neural stem cells and precursors, have been postulated for therapy. There are however complexities in obtaining neural stem cells from the adult CNS; this obviously does not pose a problem for embryonic stem cells. A group from the University of California, San Francisco, published their findings in The Scientist (July 2007) cautioning against the notion that neural stem cells can regenerate into any type of neuron.
This group has revealed that it is possible for scientists to manipulate neural stem cells in vitro to make them more flexible, hence more likely to regenerate into the type of neural cell that one is trying to repair. Our team will only utilise neural stem cells that have already shown the ability in vitro to regenerate into glial cells and thus will remyelinate the damaged axons once injected into patients.
Almost ten years ago adult bone marrow cells were shown to have the ability to differentiate to oligodendroglial cells, indicating their suitability for treating demyelinating diseases. At the same time, a phase II trial utilising autologous bone marrow stem cell transplantation to treat 85 patients for progressive multiple sclerosis was conducted in 20 European centres. Neurological improvement was recorded in 21% of patients; confirmed progression-free survival was documented in 74% of patients at 3 years; disease progression was reduced to only 20%.
Additionally, it was reported that autologous haematopoietic stem cell transplantation treatments could regenerate a tolerant immune system and become a potentially effective rescue therapy for the subset of patients with aggressive forms of multiple sclerosis, refractory to existing immunomodulatory and immunosuppressive agents. Cassiani-Ingoni and fellow investigators, suggest that bone marrow stem cell transplantation can suppress the autoimmune inflammatory disease in the majority of multiple sclerosis patients, but is able to retard the clinical progression only in patients who were treated during the early stages of the disease.
(Mesenchymal stem cells are non-haematopoietic stem cells derived from marrow or umbilical cord). Evidence supports that mesenchymal stem cells have the ability to generate cells with the characteristics of neurons and glial cells and consequently promote repair within the injured CNS. How mesenchymal stem cells lead to functional recovery in the damaged adult CNS is not clearly determined. It is postulated that transplanted multipotent cells migrate to the injury sites, proliferate, and then differentiate into the appropriate neural cells, which then leads to neural repair and regeneration.
Although mesenchymal stem cells possess high survival and migration potential, the proportion that may be directed towards neural differentiation appears to be relatively small. Mesenchymal stem cells, perhaps via the release of soluble neurochemical signals at the origin of neural damage, exert a direct influence on the endogenous neural stem cells to promote repair through neuro- and oligodendrogenesis.
Mesenchymal stem cells also exert immunomodulatory effects through inducing suppression of the autoimmune myelin-targeting lymphocytes. Mesenchymal stem cells can be harvested from the bone marrow of the patient, thereby reducing the risk for developing reactions.
CD34+ stem cells are multipotent haematopoietic stem cells found in bone marrow and umbilical cord. These stem cells are capable of transforming into neuroprotective glial and myelin-producing oligodendrocytes (10). A proposed advantage of umbilical cord CD34+ stem cell transplantation is that, when administered, virtually no side effects are evident (10).
There are numerous anecdotal results for treatment of multiple sclerosis with stem cells. Many of the anecdotal reports reveal remarkable benefit from stem cell treatment for the disease. Since this condition does fluctuate many critics are not convinced that these benefits are derived from stem cell treatment.
To date there have been no ‘gold standard’ randomised double blind placebo controlled trials. Many stem cell treatments are performed in small clinics where the results are not documented and validated, or are from completely unregulated clinics in third world countries.
See References (below) for other trials into treatment with stem cells for multiple sclerosis.
Significant advances are being made daily in researching the therapeutic potential of stem cells for neurodegenerative diseases. There are already several facilities offering stem cell treatments but before proceeding with any treatment please discuss this with your treating neurologist or our stem cell experts.
Transplanting stem cells into focal multiple sclerosis lesions will be the ultimate therapeutic approach, although this will involve a neurosurgical procedure. Clinical trials are needed to determine whether exogenous stem cells are able to survive, differentiate and myelinate axons in plaques. If you would like to be considered for a clinical trial please contact our research trials coordinator.
Multiple sclerosis is a multifocal inflammatory disease of the central nervous system, which affects young individuals and causes paralysis of the limbs, sensation, visual and sphincter problems. The estimated incidence is 1 in 1000 in the US and Europe. It is also more prevalent in colder climates and has become the commonest neurodegenerative disease as its incidence is rising.
The disease is caused by an autoimmune mechanism, i.e. the immune system produces antibodies and cells which attack the self myelin antigens, thereby causing demyelination. Demyelination occurs via a process of gradual destruction of the myelin sheath, which surrounds the axons (neural network) of nerve cells (neurons), leading to axonal injury and consequently severely impaired nerve conduction with its neurological conditions as a result of the disease process.
The disease derives its name from the multiple scleroses (scars or plaques) that are created on the myelinated axons. This damage occurs in patches that appear as distinct lesions at MRI. Recurrent episodes of demyelination eventually deteriorate the myelin sheath with repeated remyelinations causing scarring and deterioration of the functioning of the axons. Regeneration of the myelin sheath occurs via remyelination of the axons mediated through cells known as oligodendrocytes and oligo-dendritic stem cells. This only takes place in the early phases of the disease but electron micrographic evidence has revealed that the regenerated myelin sheaths are thinner and less effective at nerve conduction.
The disease is clinically evident with relapses of neurological disability due to the dysfunction of the areas (plaques of multiple sclerosis) in which damage of myelin occurs. Disability can accumulate with time and the disease enters a progressive phase due to damage of the axons and irreversible neurodegeneration. This is why treatment for multiple sclerosis has to be instigated as early as possible to prevent permanent damage of the neurons, which is very difficult to treat.
With progression of the disease the central nervous system becomes unable to recruit oligodendrocyte stem cells, but it is unclear why this appears to be inhibited with longstanding disease. Perhaps it is due to secondary auto immune inflammatory responses. Once again the benefits of treatment are obviously greater the sooner the treatment is initiated.
Multiple sclerosis causes a myriad of symptoms depending on where in the central nervous system the lesions occur. Neurological deficits inexorably and progressively accumulate causing worsening of the clinical picture. Unfortunately there are numerous complicating factors resulting in the unpredictable course of the disease. This makes it very difficult to give prognosticators of disease progression. There are periods of dormant activity followed by periods of unpredictable exacerbations, during which there is steady progression of the disease process with the resultant decline in neurological function, eventually leading to intractable neurological disability.
1. Magnus, Rao et al. Neural stem cells in inflammatory CNS diseases: mechanisms and therapy J. Cell. Mol. Med. (2005) 9:2 303-319
2. Duncan I Replacing cells in multiple sclerosis J.Neurol.Sci. Jun 2007 (epub ahead of print
3. Bai, Caplan, Lennon & Miller Human Mesenchymal Stem Cells Signals Regulate Neural Stem Cell Fate Neurochem Res (2007) 32:353:362
4. Miller & Bai. Cellular approaches for stimulating CNS remyelination Regenerative medicine 2007 Sept 2 (5) 817-829
5. Karussis, Kassis, Basan, Slavin. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells: a proposed treatment for MS J.Neurol.Sci 2007 July (epub ahead of print)
6. Bonilla, Alarcon, Villaverde et al Eur J Neurosci 2002 15(3) 575-582.
7. Muraro, Bielekova Emerging therapies for MS,. Neurotherapeutics 2007 Oct 4(4) 676-692
8. Cassiani-Ingoni, Muraro, Magnus et al. Disease progression in a model of MS J.Neuropathol Exp Neurol 2007 Jul 66(7);637-49
9. Karussis & Kassis. Use of stem cells for the treatment of MS Expert Review of eurotherapeutics 2007Sept: 7(9) 1189-1201
10. J Neurol Sci. 2008 Feb 15;265(1-2):136-9. Epub 2007 Sep 29. Can we pass from the experimental to the clinical phase in MS stem cell research? Hommes OR.
11. J Neurol Sci. 2008 Feb 15;265(1-2):111-5. Epub 2007 Sep 27.Autologous mesenchymal bone marrow stem cells: practical considerations. Scolding N, Marks D, Rice C.
The anecdotal reports of the results of stem cell treatment for cerebral palsy are extraordinary. However, none have yet been published in peer-reviewed journals as the clinics providing these treatments have generally been functioning without legal approval, or worse, are still without any regulatory framework whatsoever. In order to remedy this and provide knowledge for all, Tissu only conducts treatment under strict clinical trial protocols and guidelines. All of our results are available and transparent. The patients that have been given stem cells for cerebral palsy range from newborns to adults. It is believed that giving the treatment earlier in life or earlier in the course of the disease leads to better results.
An eight-week regimen of injections of neural stem cells into a 19-year-old patient’s spinal fluid relieved many of the debilitating symptoms of cerebral palsy,
The stem cells were introduced into a Hungarian patient’s (19-year-old Gabor Bocskai) spinal cord fluid via a lumbar puncture. These neural stem cells then migrated to the brain and started the unbelievable treatment.
“Unedited videos taken before and after [the patient’s] injections dramatically demonstrate the profound improvement in his 19-year battle to walk, write, focus his eyes, concentrate, and overcome the many other detrimental effects resulting from the cerebral palsy, he acquired at birth,” the hospital said.
Improvements included improved vision, increased eye focus and better concentration on one subject.
“He also reported clearer writing, enhanced muscle tone, the ability to sit up unsupported, and a new capability to walk and swim in an unassisted manner,” the hospital said. “As a lifelong quadriplegic with paralysis in his lower limbs, he was never able to walk independently, using a wheelchair for transportation. Within four months of the initial treatment, he stated that he was able to walk with the help of a walker and no other support, and at a rate three times faster than ever before with increased manoeuvrability in his legs and torso. Even his speech became clearer and faster.”
The hospital said the patient has returned to Hungary from the treatment centre and has reported “continued daily improvement.”
It is cautioned, however, that not every teenage cerebral palsy patient treated with stem cell therapy should expect the same results.
The treatment program for cerebral palsy sufferers centres on a stem cell treatment that includes approximately four injections of neural stem cells into the spinal cord fluid via a lumbar puncture.
“For 2-year-old Chloe Levine, life was not easy. From her birth, she was suffering from an incurable disease called cerebral palsy. Her only hope was stem cell therapy.
Her parents had saved her umbilical cord blood at the time of her birth. It was the stem cells that saved her from the deadly disease. This two year old toddler was infused with stem cells from her own umbilical-cord blood. It saved her from the condition. She was able to use her right hand.“
Cerebral palsy (CP) is defined as any non-progressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Cerebral palsy (CP) is a large group of disorders impairing control of movement due to a defect or lesion of the developing brain. Symptoms become apparent within the first few years of life and generally do not worsen over time [Hughes and Newton, 1992].
Cerebral palsy is a common disorder of childhood, with an incidence of 1 in 250 to 1,000 births [Bundey and Alam, 1993; Pharoah et al., 1987]. Individuals with cerebral palsy may have difficulty in fine motor skills, maintaining balance and walking, or have involuntary movements such as uncontrollable writhing motions of the hands or drooling. Some patients may also have mental retardation and seizures, and some children with cerebral palsy are born with an abnormally small head (microcephaly) [NINDS, 2005].
A study of cerebral palsy prevalence in Asian (almost exclusively from Northern Pakistan) and non-Asian populations in Yorkshire, United Kingdom has reported a two-fold increase in cerebral palsy prevalence in the Asian population (6.42 cases per 1,000) compared to non-Asian population (3.18 cases per 1,000) [Sinha et al., 1997]. Since about 60 % of the Asian families in this study had a known history of consanguineous marriages, and since about a third of the affected children in these families had a first or second degree relative with the same type of cerebral palsy, recessive genes may have caused the increased incidence.
An independent study from Saudi Arabia reported a 2.5-fold increase in the occurrence of cerebral palsy in consanguineous families [Al-Rajeh et al., 1991], also strongly suggesting that the recessive forms of CP exist.
Cerebral palsy is divided into four main categories: spastic, athetoid, ataxic, and mixed forms, according to the type of movement disturbance [Hughes and Newton, 1992; NINDS, 2005]. Spastic cerebral palsy accounts for approximately 70-80% of cases, and is subdivided into hemiplegic, diplegic, quadriplegic, and monoplegic types, depending on which limbs are affected. The most severe form of spastic cerebral palsy, spastic quadriplegia, is frequently accompanied by dysarthria (abnormal speech characterised by poor articulation). The most common mixed forms are spasticity and athetoid (abnormal) movements, but other combinations are also possible [NINDS, 2005].
The movement and posture abnormalities that are characteristic of cerebral palsy are associated with underlying abnormalities of muscle tone, including dystonia, spasticity, and rigidity. The subtypes of cerebral palsy are defined according to the predominant muscle tone abnormality, its distribution and severity. There is widespread agreement that cerebral palsy subtypes should be divided into the following groups: spastic subtypes (hemiplegia: unilateral asymmetric spasticity; diplegia: bilateral symmetric spasticity, lower limbs more affected than upper limbs; quadriplegia: bilateral symmetric spasticity, upper and lower limbs affected equally), dystonic or athetotic type; and other miscellaneous types: hypotonic, mixed types, etc. These descriptive definitions are not useful when forming cohorts of cerebral palsy subtypes in research.
The cause of cerebral palsy is often hard to determine but about 10-15% of cases appear to be due to intrapartum problems [Blair and Stanley, 1988]. The other major risk factors are prematurity, small size for gestational age, and multiple births [Stanley, 1994]. Inherited factors are thought to contribute to approximately 2% of cases in European populations [Hughes and Newton, 1992; Mitchell and Bundey, 1997]. However, with increased understanding of genetic patterns that cause neonatal brain disorders, it is clear that some patients have a genetic basis for their condition..
Cerebral palsy is a group of brain diseases that produce chronic motor disability in children. The causes are quite varied and range from abnormalities of brain development to birth-related injuries to postnatal brain injuries. Due to the increased survival of very premature infants, the incidence of cerebral palsy may be increasing. While premature infants and term infants who have suffered neonatal hypoxic–ischaemic (HI) injury represent only a minority of the total cerebral palsy population, this group demonstrates easily identifiable clinical findings, and much of their injury is to oligodendrocytes and the cerebral white matter. While the use of stem cell therapy is very promising there are no controlled trials in humans with cerebral palsy and only a few trials in patients with other neurologic disorders. However, studies with experimentally induced strokes or traumatic injuries have indicated that benefit is possible. The potential to do these stem cell transplants via injection into the vasculature or cerebrospinal fluid rather than directly into the brain increases the likelihood of timely human studies.
We have recently developed a comprehensive program for cerebral palsy patients combining both nerve stem cell activation and stimulation treatment and stem cells treatments via injections. This combined treatment has so far proved itself to be most efficient in bringing high level of recovery. By employing all of the above methods we can maximally improve functions such as mobility, language and intelligence.
3 - 4 injections of 10 million stem cells each are given to each patient into the subarachnoid space at lumbar puncture. As most cerebral palsy patients have global brain damage this treatment optimises delivery. Through the cerebrospinal fluid, the stem cells will migrate to the damaged areas in the brain. This procedure is short and simple and done with local anaesthesia. In order to prevent even the minor risk of infection and keep a strictly sterile environment, the procedure is done in the operation room by our consultant stem cell expert or radiologist.
NINDS. Cerebral Palsy: Hope Through Research. NINDS. 2005
The potential of cord blood stem cells for use in regenerative medicine Harris, David T; Badowski, Michael; Ahmad, Nafees; Gaballa, Mohamed A: Expert Opinion on Biological Therapy, Volume 7, Number 9, September 2007 , pp. 1311-1322(12)
Stem cells and neurological diseasesD. C. Hess and C. V. Borlongan: Informa Healthcare
Department of Neurology, Medical College of Georgia, and Medical Research Service, VA Medical Center, Augusta, GA 30912, USA
World-Class Stem Cell Treatment Facility Follows up Parkinson’s Successes with Another Medical Triumph, Brings New Hope of Effective Treatment for Thousands with CP, April 19, 2007—Neurosurgical Hospital, the world’s leading center for effective treatment of Parkinson’s disease and stroke, today here announced a breakthrough in the worldwide treatment of Cerebral Palsy
The Treatment of cerebral palsy: what we know, what we don’t know . M Goldstein The Journal of Pediatrics , Volume 145 , Issue 2 , Pages S42 - S46
Stem and progenitor cell−based therapy of the human central nervous system. Steve Goldman.Nature Biotechnology 23, 862 - 871 (2005)
Published online: 7 July 2005; | doi:10.1038/nbt1119
Steve Goldman Division of Cell and Gene Therapy, Departments of Neurology and Neurosurgery, 601 Elmwood Ave., Box 645, University of Rochester Medical Center, Rochester, New York 14642, USA.
Al-Rajeh, S; Bademosi, O; Awada, A; Ismail, H; Al-Shammasi, S; Dawodu, A. Cerebral palsy in Saudi Arabia: a case-control study of risk factors. Dev Med Child Neurol. 1991;33:1048–1052
Bundey, S; Griffiths, Mi. Recurrence risks in families of children with symmetrical spasticity. Dev Med Child Neurol. 1977;19:179–191
An Autosomal Recessive Form of Spastic Cerebral Palsy (CP) with Microcephaly and Mental Retardation. Anna Rajab,1,2* Seung-Yun Yoo,4,5* Aiman Abdulgalil Am J Med Genet A. 2006 July 15; 140(14): 1504–1510.
doi: 10.1002/ajmg.a.31288.
The progressive increase in life expectancy within the last century has led to the appearance of novel health related problems. Some of these are within the musculoskeletal field, for example diseases such as osteoporosis, osteoarthritis, rheumatoid arthritis and bone cancer, just to mention some of the most relevant. Other related problems are those that arise from serious injuries, often leading to non-recoverable critical joint-space defects. The therapies currently used to treat this type of diseases / injuries are based on the use of pharmaceutical agents and auto / allotransplant and synthetic materials. However, such solutions present a number of inconveniences.
The appearance of a novel field of science called tissue engineering brought some hope for arthritis sufferers. It is believed that by combining a 3D porous template scaffold with an adequate cell population, with osteo or chondrogenic potential, it will be possible to develop bone and cartilage tissue equivalents that when implanted in vivo ( back into the human body), could lead to the total regeneration of the affected area. This ideal cell population should have a series of properties, namely a high osteo and chondrogenic potential and at the same time, should be easily expandable, i.e. capable of self replicating and maintained in cultures for long periods of time. Due to their natural and intrinsic properties, stem cells are one of the best available cell types.
During the last 10 / 15 years, the scientific community witnessed and reported the appearance of several sources of stem cells with both osteo and chondrogenic potential. There are many different sources of adult stem cells (bone marrow, periosteum, adipose tissue, skeletal muscle and umbilical cord) for bone and cartilage regenerative medicine, namely those focusing on the differentiation potential of the latter, as well as in vivo proof of concept of their applicability.
Mesenchymal stem cells, the non-heamatopoietic progenitor cells found in various adult tissues, are characterized by their ease of isolation and their rapid growth in vitro while maintaining their differentiation potential, allowing for extensive culture expansion to obtain large quantities suitable for therapeutic use. These properties make mesenchymal stem cells an ideal candidate cell type to use as building blocks for tissue engineering efforts to regenerate replacement tissues and repair damaged structures as encountered in various arthritic conditions. Osteoarthritis (OA) is the most common arthritic condition and, like rheumatoid arthritis (RA), presents an inflammatory environment with immunological involvement. This has been an enduring obstacle that can potentially limit the use of cartilage tissue engineering, although clinical cases where allogeneic and autologous stem cell procedures were shown to ameliorate and potentially cure the arthritis are well documented. Phase I and Phase II clinical studies of stem cell treatments have established the feasibility, safety and efficacy of autologous stem cell mobilisation and transplantation.
Recent advances in our understanding of the functions of mesenchymal stem cells have shown that they also possess potent immunosuppression and anti-inflammation effects. In addition, through secretion of various soluble factors, mesenchymal stem cells can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in arthritis. This function of mesenchymal stem cells can be exploited for their therapeutic application in degenerative joint diseases such as rheumatoid arthritis and osteoarthritis(1)
Although cartilage defects are common features of osteoarthritis and rheumatoid arthritis, current medical treatments can rarely restore the full function of native cartilage. Recent studies have provided new perspectives for cartilage engineering using multipotent mesenchymal stromal stem cells. Moreover, mesenchymal stromal stem cells have been used as immunosuppressant agents in autoimmune diseases and have tested successfully in animal models of arthritis.
Mesenchymal stromal stem cells extracted from the patient’s own bone marrow are sent for various laboratory tests and cell culture to grow sufficient cells, which are then used to stimulate cartilage regeneration via two techniques – an open or a minimally invasive procedure.
The open technique involves opening the knee joint and implanting the stem cells into the affected area. For the minimally invasive technique, cultured stem cells are injected into the knee three weeks after an initial arthroscopic microfacture, which is a surgical technique to treat damaged areas of the knee’s articular cartilage.
The advantages of stem cell transplantation and cartilage regeneration:
Cartilage defects have a poor healing capacity, and unresolved injury tends to progress to osteoarthritis. Until recently, the treatment for such problems was limited to surgical methods that involved the abrasion and drilling of the subchondral bone in the knee. This technique stimulates repair tissue, which unfortunately degenerates with time. Tissue engineering using stem cells for cartilage regeneration has been found to be promising.
Mesenchymal stem cells are able to grow into various mesenchymal cells, such as cartilage and secrete bioactive factors that help the healing process in the knee. Mesenchymal stem cells grow faster than cartilage cells, reducing the culture incubation period in the laboratory. This technique also averts the need to harvest cartilage, lowering donor site morbidity.
Mesenchymal stem cells from rheumatoid arthritis and osteoarthritis patients possess similar chondrogenic potential as mesenchymal stem cells isolated from healthy donors. Therefore, these cells may serve as a potential new prospect in cartilage replacement therapy.
Immunoablative therapy and heamatopoietic stem cell transplantation is an intensive treatment modality aimed at ‘resetting’ the dysregulated immune system of a patient with immunoablative therapy and allow outgrowth of a nonautogressive immune system from reinfused heamatopoietic stem cells, either from the patient (autologous stem cells) or a healthy donor (allogeneic stem cells).
Autologous stem cells have been shown to induce profound alterations of the immune system affecting B and T cells, monocytes, and natural killer cells and dendritic cells, resulting in elimination of autoantibody-producing plasma cells and in induction of regulatory T cells.
Most of the available data has been collected through retrospective cohort analyses of autologous stem cell treatments, case series, and translational studies in patients with refractory autoimmune diseases. Long-term and marked improvements of disease activity have been observed, notably in systemic sclerosis, systemic lupus erythematosus, and juvenile idiopathic arthritis, and treatment-related morbidity has improved due to better patient selection and modifications of transplant regimen.
Mesenchymal stem cells - isolated from various tissues in humans and other species - are one of the most promising adult stem cell types due to their availability and the relatively simple requirements for in vitro expansion. They have the capacity to differentiate into several tissues, including bone, cartilage, tendon, muscle and adipose, and produce growth factors and cytokines that promote hematopoietic cell expansion and differentiation. In vivo, mesenchymal stem cells are able to repair damaged tissue from kidney, heart, liver, pancreas and gastrointestinal tract. Furthermore, they also have anti-proliferative, immunomodulatory and anti-inflammatory effects, but evoke only little immune reactivity. Although the mechanism underlying the immunosuppressive effects of mesenchymal stem cells has not been clearly defined, their immunosuppressive properties have already been exploited in the clinical setting. Therefore, in the future, MSCs might have implications for treatment of allograft rejection, graft-versus-host disease, rheumatoid arthritis, autoimmune inflammatory bowel disease and other disorders in which immunomodulation and tissue repair are required
The word arthritis means joint inflammation. The term arthritis is used to describe more than 100 rheumatic diseases and conditions that affect joints, the tissues which surround the joint and other connective tissue. The pattern, severity and location of symptoms can vary depending on the specific form of the disease. Typically, rheumatic conditions are characterized by pain and stiffness in and around one or more joints. The symptoms can develop gradually or suddenly. Certain rheumatic conditions can also involve the immune system and various internal organs of the body.
Types of arthritis
A brief overview of the most common forms of arthritis will be discussed in this section.
In 2006, the combined data from the National Health Interview Survey years 2003–2005 Sample Adult Core estimated an average yearly prevalence of arthritis in American adults to be 21.6% (46.4 million). This disease is more common in women than in men and increases with age.
There is much disagreement among experts about definitions of childhood arthritis. At least three clinical classification schemes exist: juvenile rheumatoid arthritis (JRA), juvenile chronic arthritis (JCA), and juvenile idiopathic arthritis (JIA). All three schemes do not include many of the conditions considered as arthritis and other rheumatic conditions in adults. Also, a case counted in one classification system may not be a case in another system. However, all schemes define childhood arthritis as occurring in people younger than 16 years. The most common form of juvenile arthritis is juvenile rheumatoid arthritis (the term and classification system used most commonly in the United States). Juvenile rheumatoid arthritis involves at least 6 weeks of persistent arthritis in a child younger than 16 years with no other type of childhood arthritis. Juvenile rheumatoid arthritis has three distinct subtypes: systemic (10%), polyarticular (40%) and pauciarticular (50%). Each type has a unique presentation and clinical course and immunogenetic association. For the latter two types, girls are more commonly affected (3–5:1). In all three types about 40 – 45% still have active disease after 10 years. For the systemic type, the peak age of onset is 1 to 6 years old and about 50% of cases show very short stature in adulthood as a result. For the pauciarticular form, there are two distinct subtypes: early onset and late onset. Early onset is more common in girls, late onset is more common in boys. The genetics differ as do the clinical courses. In the polyarticular form, there are also two subtypes: rheumatoid factor (RF) positive and negative. RF positive usually affects girls with onset after 8 years of age and a poorer prognosis compared with RF negative children
Rheumatoid arthritis (RA), an autoimmune condition, is a chronic inflammatory polyarthritis.1
Natural history studies of RA suggests that RA follows one of three courses:
Another natural history study found that 75% of people with RA experienced remission after five years.
The current status of stem cell transplantation for treatment of rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, and systemic sclerosis are varied. From a large European bone marrow transplant registry, a bird’s eye view of stem cell transplantation for autoimmune disease can be obtained. Among 43 rheumatoid arthritis patients, 35 juvenile chronic arthritis patients, 34 systemic lupus erythematosus patients and 58 systemic sclerosis patients who underwent stem cell transplantation, initial responses in most patients were good to excellent. In rheumatoid arthritis and systemic lupus erythematosus treatment, the criteria for patient selection are still not clear and the therapeutic regimens for stem cell transplantation (and whether follow-up treatment is necessary) are not fully defined. In juvenile chronic arthritis, responses are encouraging although little fully published data beyond that from the European Bone Marrow Transplant Registry exists.
Cellular immune therapy for severe autoimmune diseases can now be considered when such patients are refractory to conventional treatment. The use of autologous stem cell transplantation to treat human autoimmune diseases has been initiated following promising results in a variety of animal models. Anecdotal observations have been made of autoimmune disease remission in patients who have undergone allogeneic bone marrow transplantation as a result of coincidental haematological malignancies. The possibility of inducing immunological self-tolerance by autologous stem cells is particularly attractive as a means for treating juvenile idiopathic arthritis.
Mesenchymal stem cells are precursors of tissue of mesenchymal origin, but they also have the capacity to regulate the immune response by suppressing T and B lymphocyte proliferation in a non-major histocompatibility complex-restricted manner. Use of stem cells as immunosuppressant agents in autoimmune diseases has been proposed and successfully tested in animal models. The feasibility of using allogeneic mesenchymal stem cells as therapy for collagen-induced arthritis, a mouse model for human rheumatoid arthritis, has already been convincing. A single injection of mesenchymal stem cells prevented the occurrence of severe, irreversible damage to bone and cartilage. Mesenchymal stem cells induced hyporesponsiveness of T lymphocytes as evidenced by a reduction in active proliferation, and modulated the expression of inflammatory cytokines. In particular, the serum concentration of tumor necrosis factor alpha was significantly decreased. These results suggest an effective new therapeutic approach to target the pathogenic mechanism of autoimmune arthritis using allogeneic mesenchymal stem cells.
Osteoarthritis is a chronic joint disorder in which there is progressive softening and disintegration of articular cartilage, accompanied by new growth of cartilage and bone at the joint margins (osteophytes) and capsular fibrosis. The common cause of osteoarthritis are genetic conditions, metabolic,hormonal and mechanical injury. Most importantly, ageing degenerative joint disease is by far the commonest form of arthritis, characterized by focal and progressive loss of the hyaline cartilage of joints, underlying bony changes that are clearly identified on radiographic changes (joint space narrowing, osteophytes and bony sclerosis).
Mesenchymal stem cells in arthritic diseases.
Chen FH, Tuan RS.
Arthritis Res Ther. 2008 Oct 10;10(5):223. [Epub ahead of print]
PMID: 18947375
Stem cell transplantation for rheumatic autoimmune diseases.
Hügle T, van Laar JM.
Arthritis Res Ther. 2008 Oct 10;10(5):217. [Epub ahead of print]
PMID:
Mesenchymal stem cells: a future for the treatment of arthritis?
Swart J, Martens A, Wulffraat N.
Joint Bone Spine. 2008 Jul;75(4):379-82. Epub 2008 Jun 16. No abstract available.
PMID: 18558507
Multipotent mesenchymal stromal cells in articular diseases.
Jorgensen C, Djouad F, Bouffi C, Mrugala D, Noël D.
Best Pract Res Clin Rheumatol. 2008 Apr;22(2):269-84. Review.
PMID: 1845568
Adult stem cells in bone and cartilage tissue engineering.
Salgado AJ, Oliveira JT, Pedro AJ, Reis RL.
Curr Stem Cell Res Ther. 2006 Sep;1(3):345-64. Review.
PMID: 18220879
Autologous haematopoietic stem cell transplantation in juvenile idiopathic arthritis
L Wedderburn, M Abinun, P Palmer, and H Foster
Rheumatology Unit, Institute of Child Health, UCL and Great Ormond Street Hospital NHS Trust, London, UK. Email:
Currently there is no form of therapy to cure autism. Modern treatments and therapies for autism include medical (treatment of anxiety and depression), nutritional (restriction of allergy-associated dietary components / supplementation of minerals and vitamins / antioxidant therapy) and behavioural. None are curative. Research has been slow and interested in the neurophysiology between the immune system and the nervous system.
The rationale for stem cells treatment for autism lies in the administration of CD34+ umbilical cord cells and mesenchymal cells. It is theorised that these cells may help the hypoperfusion of the brain and immune malfunction. Treatment with these stem cells together may potentially improve both the brain and the gut in these patients with autism. Anecdotal results from the treatment of autistic children in some clinics are very encouraging.
The use of umbilical cord blood CD34+ stem cells in autism is due to the fact that these cells have a role to play in angiogenesis. This is the formation of new and collateral blood vessels and is necessary for brain recovery. It is this fact that makes CD34+ Haemopoietic stem cells so useful in the treatment of neurodegenerative diseases. The infusion of CD34+ vascular progenitor stem cells from umbilical cord blood may lead to new vessel formation. Consequently improved blood flow and oxygen to the brain should improve nervous system functioning and this should theoretically improve autistic patients. Safety concerns regarding allogeneic (another individuals) CD34+ cells; in particular fears of graft versus host reactions have not been borne out. Riordan et al (6) have recently published an account of the safety and feasibility of cord blood cells administration in absence of immune suppression, i.e. without the need for suppressing an individual’s immune response. There are numerous reports of stem cell treatments where no immune suppression was used; one study followed up 500 patients without a single one suffering graft vs. host reaction.
Mesenchymal stem cells alter the immune system in the brain. Research data suggests that this will influence neurological function profoundly. The ability of mesenchymal stem cells to suppress pathological immune responses (e.g. inflammation) and to stimulate haematopoiesis and angiogenesis (blood cell regeneration) suggests that these mesenchymal stem cells may be useful for treatment of the defect in T cell numbers associated with autism. This is another area of active research within our group.
It is believed that the use of combination therapy utilising CD34+ stem cells and mesenchymal stem cells may induce synergistic effects in the treatment of neurological diseases. We propose to treat autistic patients with both these types of stem cells, as our experience suggests that treatment with only one type of stem cell is not clinically efficacious.
While the rationale for using stem cells to treat autism is sound and many anecdotal cases suggest significant improvement, almost all proponents of stem cell treatment for autism are in agreement that more clinical trials are needed to assess treatment efficacy. When patients and their families consider new treatments, the proposals need to be interpreted in a discerning manner that can be balanced with scientific evidence. Patients considering this therapy should ensure that they consult fully with their own doctor and specialist to make sure that they are getting optimal treatment with the appropriate combination of CD34+ stem cells and mesenchymal stem cells.
Autism is a neurological developmental disorder, characterised by a number of abnormalities that includes poor social interactions, communication difficulties, obsessive attachment to routines and repetition, and often an extreme dislike of certain sounds, textures and tastes. Autism usually presents within the first three years of life and is of variable severity ranging from the very mild (Asperger’s type) to chronically disabling. Evidence suggests that are two abnormalities in the brain that are seen in autism. The causes of autism are thought to be due to environmental, immunological and neurological factors. There are no specific MRI or other radiological findings.
Autism afflicts roughly 1 in 200 of the general population and this condition is also being reported as one of the fastest-growing developmental disabilities in the US, although with the advent of stem cell based interventions and treatments there may be ‘light at the end of the tunnel’. This diagnosis has reached staggering proportions in the last decade with an estimated 1.5 million children and adults in the U.S. currently (as at 2007) having some form of autism. Autism spectrum disorders such as Asperger’s Syndrome are believed to affect approximately 1 in 166 children.
The two main abnormalities which have been recognised are firstly, due to decreased perfusion in the brain and secondly, due to immune abnormalities. The decreased cerebral perfusion may cause abnormal function in the brain from hypoxia (reduced oxygen supply) and by decreased cell membrane function, causing the build up of abnormal substances (metabolites or neurotransmitters).
It is thought that if perfusion can be improved through the growth of new blood vessels (angiogenesis), then this should also allow better perfusion as well as enhanced metabolite clearance and restoration of brain function.
In addition there is an abnormality of the immune system seen in autism. In autism, it is thought that an autoimmune response against the brain’s own self causes part of the loss of functioning. Astrocytes (supportive brain cells) that usually play a vital role in regulating perfusion and protection against central nervous system infection, may have the potential to affect neurodevelopment when functioning in a self destructive way. Other putative evidence for this is that autistic patients often demonstrate chronic inflammation amongst other organs, such as the stomach as well as the central nervous system.
1. Review: Stem Cell Therapy for Autism Thomas Ichim, Fabio Solano, Eduardo Glenn, Frank Morales, Leonard Smith, George Zabrecky, Neil H Riordan Journal of Translational Medicine June 2007, 5:30 http://www.translational-medicine.com/content/5/1/30
2. Alliance for stem cell research http://www.curesforcalifornia.com
3. The immune response in autism: a new frontier for autism research Paul Ashwood, Sharifia Wills, Judy vd Water Journal of Leukocyte Biology. 80:1–15; 2006
4. The Stem Cell and Autism Connection http://www.bodyecology.com
5. Autism http://www.stemcelltherapies.org
6. Cord blood in regenerative medicine: do we need immune suppression? Riordan N, Chan K, Marleau A, Ichim T. Journal of Translational Medicine. Jan 2007 5:8
7. http://www.autismvox.com/another-autism-treatment-stem-cell-therapy Kristina Chew, July 2007
8. http://www.cellmedicine.com (publication is equivalent to Review: Stem Cell Therapy for Autism Ichim et al.)
9. Osiris http://www.osiris.comhttp://www.translational-medicine.com/content/5/1/30
In the last few years, two significant scientific milestones have emerged. The first was the finding of the existence of central nervous system neural stem cells. This has led to a new way of thinking about the brain, as previously scientists believed the brain was not capable of regeneration. And the second was the isolation, expansion and manipulation of human stem cells.
In neurological disorders where cells are lost focally such as in Parkinson’s disease, the use of stem cells to treat the accompanying symptoms is thought to have great potential. However, the greater extent of neuronal cell loss in dementia, and in Alzheimer’s disease in particular, means that the use of stem cell therapy for the treatment of Alzheimer’s disease is less well understood. There are numerous reports of improvements in functioning in Alzheimer’s disease following stem cell treatments; these remain unverified, however. For this reason Tissu intends to document all its results.
If neurons that are lost can be replaced then it is assumed that mental deterioration can be halted and possibly reversed. Tissu carefully assesses which cells are used for stem cell treatment and for this reason our approach is to use stem cells that have commenced differentiation into adult neural stem cells for Alzheimer’s disease. The use of adult mesenchymal stem cells is of great benefit, overcoming ethical issues and problems of possible immune reaction.
Currently there are no medicines that can slow the progression of Alzheimer’s disease. However, four FDA-approved medications are used to treat Alzheimer’s disease symptoms. These drugs help individuals carry out the activities of daily living by maintaining thinking, memory, or speaking skills. They can also help with some of the behavioral and personality changes associated with Alzheimer’s disease. However, they will not stop or reverse the process and appear to help individuals for only a few months to a few years. Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) are prescribed to treat mild to moderate Alzheimer’s disease symptoms. Donepezil was recently approved to treat severe Alzheimer’s disease as well. The newest Alzheimer’s disease medication is memantine (Namenda), which is prescribed to treat moderate to severe Alzheimer’s disease symptoms.
So it would seem that the brain has the capability to repair itself. Experiments in animal models of Alzheimer’s disease and Parkinson’s disease have shown that there is an up-regulation in number and subsequent migration of neural stem cells from the subventricular zone to the disease area. Also, a recent study has provided the first evidence that regenerative mechanisms may be active in the adult human brain in response to trauma or neurodegenerative processes. Post-mortem analysis of the hippocampus in a small cohort of Alzheimer’s disease patients indicated a significant increase in neurogenesis and the more severely affected patients displayed the most significant increases in newly generated hippocampal neurons. This endogenous neural stem cells ‘movement’ may be a mechanism to the neuronal degeneration in all these conditions that may lead to an improvement in patients functioning.
Alzheimer’s disease is an age-related, degenerative chronic brain disorder that develops over a period of years. Initially, people experience memory loss and confusion, which may be mistaken for the kinds of memory changes that are sometimes associated with normal aging. However, the symptoms of Alzheimer’s disease gradually lead to behavioural and personality changes, a decline in cognitive abilities such as decision-making and language skills, and problems recognizing family and friends. Eventually this leads to a severe loss of mental function. These losses are related to the worsening breakdown of the connections between certain neurons in the brain and their eventual death.
It is the most common cause of dementia among people age 65 and older. In dementia, neurons are lost throughout the brain - for example, the cortex, especially its frontal, parietal and temporal areas, the basal ganglia and the hippocampus - resulting in a general mental deterioration. If these neurons could be replaced it is hypothesised that mental deterioration could be halted and possibly reversed. Stem cell treatments provide a potential means of accomplishing this goal. Stem cell treatments may also therefore help senile dementia.
There are three major abnormalities in the brain that are associated with the disease process of Alzheimer’s:
In a very few families, people develop Alzheimer’s disease in their 30s, 40s, and 50s. This is known as “early onset” Alzheimer’s disease. These individuals have a mutation in one of three different inherited genes that causes the disease to begin at an earlier age. More than 90 percent of Alzheimer’s disease develops in people older than 65. This form of Alzheimer’s disease is called “late-onset” Alzheimer’s disease, and its development and pattern of damage in the brain is similar to that of early-onset Alzheimer’s disease. The course of this disease varies from person to person, as does the rate of decline. In most people with Alzheimer’s disease, symptoms first appear after age 65.
We don’t yet completely understand the causes of late-onset Alzheimer’s disease, but they probably include genetic, environmental, and lifestyle factors. Although the risk of developing Alzheimer’s disease increases with age, Alzheimer’s disease and dementia symptoms are not a part of normal aging. There are also some forms of dementia that aren’t related to Alzheimer’s disease, but are caused by systemic abnormalities in the small blood vessels and other disease processes.
In conclusion, stem cells provide a very appealing approach for the treatment of neurodegenerative diseases and brain injury. There have been many groundbreaking studies highlighting their exciting therapeutic opportunity, but there are still numerous hurdles that need to be overcome.
Studies have demonstrated that aged animals show significant improvements in cognitive function and neurogenesis after brain transplantation of human neural stem cells or of human adult mesenchymal stem cells that have been dedifferentiated down neural pathways.
Researchers have shown for the first time that putting two specific types of neural cells directly into an aging brain can kick-start creation of brain cells linked to learning and memory.
It has been shown over the last decade that brain cells replicate, a finding that had run counter to previously accepted dogma. The area where neuron-forming stem cells perform much of this replication is the hippocampus, a part of the brain linked to memory and learning, and an area affected in older people, as well as those with Alzheimer’s disease.
Eriksson, PS, Perfilieva, E, Björk-Eriksson, T, Alborn, A-M, Nordborg, C, Peterson and Gage, FH, (1998) Neurogenesis in the adult human hippocampus. Nat. Med. 4, 1313-1317
Jin, K, Peel, AL, Mao, XO, Xie, L, Cottrell, BA, Henshall, DC, and Greenberg, DA, (2004) Increased hippocampal neurogenesis in Alzheimer’s disease. Proc. Nat. Acad. Sci, USA 101, 343-347
Johansson, CB, Momma, S, Clarke, DL, Risling, M, Lendah, U, and Frisén, J (1999) Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System. Cell 96, 25-34
Kokaia, Z, and Lindvall, O, (2003) Neurogenesis after ischaemic brain insults. Curr Opin. Neurobiol. 13(1), 127- 132
Sanai, N, Tramontin, AD, Quiñones-Hinojosa, A, Barbaro, NM, Gupta, N, Kunwar, S, Lawton, MT, McDermott, MW, Parsa, AT, Verdugo, JM-G, Berger, MS and Alvarez-Buylla, A, (2004) Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature 427, 740-744
Activating stem cells may treat Alzheimer’s Janice Hopkins Tanne BMJ. 2005 March 19; 330(7492): 622.
Possible use of autologous stem cell therapies for Alzheimer’s disease. Sugaya K 1: Curr Alzheimer Res. 2005 Jul;2(3):367-76
Stem cells in dementia Dr Antigone EkonomouThe Journal of Quality Research in Dementia, Issue 1
Dr Antigone Ekonomou Postdotoral Research Assistant, King’s College London, The Wolfson CARD, The Wolfson Wing, Hodgkin Building, Guy’s Campus, London SE1 1UL.
Alzheimer’s Association: www.alzheimers.org.uk
Surrounding neurons with healthy adjoining cells completely stops motor neuron death in some cases. Hence stem cell transplantation might represent a promising therapeutic strategy.
Stem cell treatment for ALS / Motor Neuron disease is still rather in its infancy but results of successful treatment are very promising, with patients having increased life span following treatment.
With the lack of effective drug treatments for amyotrophic lateral sclerosis, stem cell research has highlighted this disease as a candidate for stem cell treatment. Stem cell transplantation is an attractive strategy for neurological diseases and early successes in animal models of neurodegenerative disease generated optimism about restoring function or delaying degeneration in human beings. Autologous or allogeneic stem cells are the candidate source for local or systemic cell-therapies in ALS. Stem cells isolated and expanded in culture can be modified to release growth factors and generate glial cells following transplantation into the spinal cord or brain. As such, they might be able to both detoxify the local environment around dying motor neurons and deliver atrophic factors.
In a recent study patients received intraspinal injections of autologous mesenchymal stem cells at the thoracic level and were monitored for four years. No significant side effects were evident. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. Four patients showed a significant slowing down of their respiratory function and improvement in their quality of life scores.
Our results seem to demonstrate that MSCs represent a good chance for stem cell based therapy in ALS and that intraspinal injection of MSCs is also safe in the long term. Recently it has been shown in animal models of amyotrophic lateral sclerosis that stem cells significantly slow the progression of the disease and prolong survival. All of our patients with ALS are treated under the protocols of a clinical trial in order to document the results for future patients.
Amyotrophic lateral sclerosis is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. Its symptoms are caused by the death of the anterior horn cell in the spinal cause.
The reason behind this is unknown; it is thought that reactive astrogliosis and microglia activation may play a role in causing this disease.
Motor neurons are nerve cells located in the brain, brainstem, and spinal cord that control and communicate between the nervous system and the voluntary muscles of the body. In ALS, both the upper motor neurons and the lower motor neurons degenerate or die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, waste away (atrophy), and twitch (fasciculation) because of degeneration. Eventually, the ability of the brain to start and control voluntary movement is lost.
The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; slurred and nasal speech; or difficulty chewing or swallowing. These general complaints then develop into more obvious weakness or atrophy that may cause a physician to suspect ALS.
The parts of the body affected by early symptoms of ALS depend on which muscles in the body are damaged first. In some cases, symptoms initially affect one of the legs, and patients experience awkwardness when walking or running or they notice that they are tripping or stumbling more often. Some patients first see the effects of the disease on a hand or arm as they experience difficulty with simple tasks requiring manual dexterity, such as buttoning a shirt, writing, or turning a key in a lock. Other patients notice speech problems.
Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Patients have increasing problems with moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia), including an overactive gag reflex. An abnormal reflex commonly called Babinski’s sign (the large toe extends upward as the sole of the foot is stimulated in a certain way) also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations).
To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.
ALS causes weakness with a wide range of disabilities (see below). Eventually, all muscles under voluntary control are affected, and patients lose their strength and the ability to move their arms, legs, and body. When muscles in the diaphragm and chest wall fail, patients lose the ability to breathe without ventilatory support. Most people with ALS die from respiratory failure, usually within 3 to 5 years from the onset of symptoms. However, about 10 percent of ALS patients survive for 10 or more years.
Although the disease usually does not impair a person’s mind or intelligence, several recent studies suggest that some ALS patients may have alterations in cognitive functions such as depression and problems with decision-making and memory.
Although the sequence of emerging symptoms and the rate of disease progression vary from person to person, eventually patients will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. Difficulty swallowing and chewing impair the patient’s ability to eat normally and increase the risk of choking. Maintaining weight will then become a problem. Because the disease usually does not affect cognitive abilities, patients are aware of their progressive loss of function and may become anxious and depressed. A small percentage of patients may experience problems with memory or decision-making, and there is growing evidence that some may even develop a form of dementia.
Health care professionals need to explain the course of the disease and describe available treatment options so that patients can make informed decisions in advance. In later stages of the disease, patients have difficulty breathing as the muscles of the respiratory system weaken. Patients eventually lose the ability to breathe on their own and must depend on ventilatory support for survival. Patients also face an increased risk of pneumonia during later stages of ALS.
Mazzini L, Mareschi K, Ferrero I, Vassallo E, Oliveri G, Nasuelli N, Oggioni GD, Testa L, Fagioli F. Stem cell treatment in Amyotrophic Lateral Sclerosis J Neurol Sci. 2008 Feb 15;265(1-2):78-83. Epub 2007 Jun 19
Silani V, Cova L Ciammol A Polli E Lancet 2004 Jul 10-16;364(9429):200-2 Stem-cell therapy for amyotrophic lateral sclerosis
Suzuki M, Svendsen CN Trends Neurosci. 2008 Apr;31(4):192-8 Combining growth factor and stem cell therapy for Amyotrophic Lateral Sclerosis
Stem cell treatments are redefining the essence of classical medicine for a variety of conditions.
TISSU is an ethical organisation which was formed in conjunction with the Government of Seychelles to remedy the many problems seen with the numerous small, illegal stem cell clinics currently in operation around the world. Unlike other clinics all our results from all treatments will be published in peer reviewed medical journals
The Seychelles Government has fully authorised the use of stem cell treatments in its country, which will undoubtedly eventually become legalised throughout the rest of the Western world, as stem cell research continues to astound us with life changing new developments.
Stem cell research has great promise for the treatment of a variety of diseases, and stem cell therapy holds exciting prospects for continuing medical advances in the next few decades. The scientific, legal, ethical and philosophical arguments have been discussed extensively and each day we read about the emergence of these new discoveries.
Tissu operates completely legally under the auspices of the Seychelles Government and National Hospital; all the stem cells and treatment protocols are available and results are all reported in peer reviewed reputable medical journals. Our objective is to help you with stem cell treatment if you need it.
Our philosophy is that we will only treat conditions with stem cells for which there is evidence and benefit, unlike other clinics that will treat anyone provided they can pay the fees. Some of our treatments are free or considerably subsidised for those who cannot afford the full payment.
Tissu aims to provide a stem cell treatment that is a smooth, stress free journey towards treating your condition. Every detail will be taken care of, allowing you to channel all your mental energy towards recovery. Prior to treatment you will receive a certified analysis of the stem cells that will be used to treat your condition.
Tissu Stem Cell clinics provide stem cell treatments for degenerative diseases and anti-ageing treatments, using stem cells only under strictly prescribed conditions. The stem cells are carefully counted and we use around twenty million stem cells per treatment; this is why our treatments have better results compared to other clinics that use only a few thousand poor quality cells. Throughout the entire process quality and sterility is maintained from manufacture through to transport and final administration to the patient.
Treatment is delivered only by medical practitioners who are guided by the strictest of protocols and in keeping with worldwide best practice, ensuring an uncompromising level of quality care that has become the benchmark in stem cell treatment. The new hospital in the Seychelles, which will complete construction in March 2009, will be where most of the treatments will be based. Tissu also has a clinic based in the clinic suites at Eden Island. All transfers on the island are arranged by Tissu with no cost to the patient.
Our expert scientific team have already created many of the benchmarks for stem cell treatment (for example, all patients receive an MRI prior to treatment to assess the benefit of treatments), which many other clinics already aspire to follow. These protocols are used to administer the stem cells and associated growth factors to each patient.
Most patients will receive the cells into the blood system as an intravenous infusion; stem cell implantation or treatment to patients with stem cells can occur into the peripheral blood through an intravenous cannula, whilst for some cardiac conditions it is into the arterial system using an arterial catheter or, in neurological conditions, into the fluid surrounding the spinal cord via a lumbar puncture.
All treatments will be performed as outpatient treatments in the Tissu Clinic, with all of the treatments taking place in the clinic’s day procedure unit. This is a sterile environment for treatments, much like many Western hospital day-stay units. Some patients may need the use of diagnostic imaging procedures such as CT for the placement of cells; these patients will be treated either at the Seychelles Victoria Hospital or the new International Hospital.
No allergic reactions have ever been documented. Stem cells are immunologically “immature”, lacking the ability to be recognized by the immune system, making the risk of an immune reaction very unlikely.
Nevertheless, in order to ensure that you do not have any problems, all patients undergoing treatment are observed and monitored daily for 2 - 3 days at the clinic.
The stem cells are as safe as many blood products from a blood bank, as they are tested twice, before and after processing, to make sure they are free from disease and contamination before being cryopreserved. Testing is for a myriad of bacterial and viral infections including HIV, Hepatitis B and bovine spongiform-encephalitis (mad-cow disease).
