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Human Neural Stem Cells for Ischemic Stroke Treatment
Zaal Kokaia1, Vladimer Darsalia2
1Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden. Zaal.Kokaia@med.lu.se.
Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. It takes place when the brain does not receive sufficient blood supply due to the blood clot in the vessels or narrowing of vessels' inner space due to accumulation of fat products. Apart from thrombolysis (dissolving of blood clot) and thrombectomy (surgical removal of blood clot or widening of vessel inner area) during the first hours after an ischemic stroke, no effective treatment to improve functional recovery exists in the post-ischemic phase. Due to their narrow therapeutic time window, thrombolysis and thrombectomy are unavailable to more than 80% of stroke patients.Many experimental studies carried out in animal models of stroke have demonstrated that stem cell transplantation may become a new therapeutic strategy in stroke. Transplantation of stem cells of different origin and stage of development has been shown to lead to improvement in experimental models of stroke through several mechanisms including neuronal replacement, modulation of cellular and synaptic plasticity and inflammation, neuroprotection and stimulation of angiogenesis. Several clinical studies and trials based on stem cell delivery in stroke patients are in progress with goal of improvements of functional recovery through mechanisms other than neuronal replacement. These approaches may provide therapeutic benefit, but generation of specific neurons for reconstruction of stroke-injured neural circuitry remains ultimate challenge. For this purpose, neural stem cells could be developed from multiple sources and fated to adopt required neuronal phenotype.
Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. It takes place when the brain does not receive sufficient blood supply due to the blood clot in the vessels or narrowing of vessels' inner space due to accumulation of fat products. Apart from thrombolysis (dissolving of blood clot) and thrombectomy (surgical removal of blood clot or widening of vessel inner area) during the first hours after an ischemic stroke, no effective treatment to improve functional recovery exists in the post-ischemic phase. Due to their narrow therapeutic time window, thrombolysis and thrombectomy are unavailable to more than 80% of stroke patients.Many experimental studies carried out in animal models of stroke have demonstrated that stem cell transplantation may become a new therapeutic strategy in stroke. Transplantation of stem cells of different origin and stage of development has been shown to lead to improvement in experimental models of stroke through several mechanisms including neuronal replacement, modulation of cellular and synaptic plasticity and inflammation, neuroprotection and stimulation of angiogenesis. Several clinical studies and trials based on stem cell delivery in stroke patients are in progress with goal of improvements of functional recovery through mechanisms other than neuronal replacement. These approaches may provide therapeutic benefit, but generation of specific neurons for reconstruction of stroke-injured neural circuitry remains ultimate challenge. For this purpose, neural stem cells could be developed from multiple sources and fated to adopt required neuronal phenotype.
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