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.
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