Revolutionizing Stroke Recovery: Unveiling the Promise of Stem Cell Therapy (original) (raw)
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Frontiers in cellular neuroscience, 2014
Ischemic stroke remains a heavy burden for industrialized countries. The only causal therapy is the recanalization of occluded vessels via thrombolysis, which due to a narrow time window still can be offered only to a minority of patients. Since the majority of patients continues to exhibit neurological deficits even following successful thrombolysis, restorative therapies are urgently needed that promote brain remodeling and repair once stroke injury has occurred. Due to their unique properties of action, stem cell-based strategies gained increasing interest during recent years. Using various stroke models in both rodents and primates, the transplantation of stem cells, namely of bone marrow derived mesenchymal stem cells (MSCs) or neural progenitor cells (NPCs), has been shown to promote neurological recovery most likely via indirect bystander actions. In view of promising observations, clinical proof-of-concept studies are currently under way, in which effects of stem and precurs...
Stem cells for enhancing recovery after stroke: a review
2009
The potential application for stem cell therapy is vast, and development for use in ischaemic stroke is still in its infancy. Access to stem cells for research is contentious; however, stem cells are obtainable from both animal and human. Despite a limited understanding of their mechanisms of action, clinical trials assessing stem cells in human stroke have been performed.
Stem cells for brain repair and recovery after stroke
Expert Opinion on Biological Therapy, 2013
Introduction: Stroke is a major worldwide cause of death and disability. Currently, intravenous thrombolysis and reperfusion therapies, but not the socalled neuroprotectant drugs, have been shown to be effective for acute ischemic stroke. Thus, new strategies to promote brain plasticity are necessary. Stem cell administration is an attractive future therapeutic approach. Areas covered: Brain protection and repair mechanisms are activated after stroke. This article is focused on the capacity of stem cell-based therapy to enhance this postinfarct brain plasticity and recovery. Future therapeutic considerations and prospects for stroke are discussed. Expert opinion: Although cell therapy is promising in stroke treatment, mechanisms of action need to be characterized in detail. Further, the different mechanisms of axonal plasticity and remodeling involucrated in brain repair, not only in the gray but also in white matter, must be investigated through noninvasive techniques, and a multidisciplinary approach is fundamental in this.
Stand alone or join forces? Stem cell therapy for stroke
Expert Opinion on Biological Therapy, 2018
Introduction: Stroke is a major cause of mortality and disability with a narrow therapeutic window after onset. Stem cell therapy may enhance the functional and neurological outcome after stroke. Areas Covered: Regenerative medicine via stem cells stands as a novel approach for stroke therapy. In particular, bone marrow-derived mesenchymal stem cells (MSCs) have neuroprotective and anti-inflammatory properties that improve brain function after stroke. Here, we discuss the use of bone marrow-derived MSCs for stroke treatment and the safety, efficacy, and mechanism of action underlying their therapeutic effects. We also examine the discrepant transplant protocols between preclinical studies and clinical trials. Laboratory studies show the safety and efficacy of bone marrow-derived MSCs in stroke models. However, while safe, MSCs remain to be fully evaluated as effective in clinical trials. Furthermore, recognizing the multiple cell death processes associated with stroke, we next discuss the potential therapeutic benefits of a combination therapy. With preliminary results and ongoing clinical trials, a careful assessment of dosing, timing, and delivery route regimens will further direct the future of stem cell therapy for neurological disorders, including stroke. Expert Opinion: Bone marrow-derived MSCs appear to be the optimal stem cell source for stroke therapy. Optimizing dosing, timing, and delivery route should guide the clinical application of bone marrow-derived MSCs.
Cellular and Molecular Life Sciences, 2009
Recent work has focused on cell transplantation as a therapeutic option following ischemic stroke, based on animal studies showing that cells transplanted to the brain not only survive, but also lead to functional improvement. Neural degeneration after ischemia is not selective but involves different neuronal populations, as well as glial and endothelial cell types. In models of stroke, the principal mecha-nism by which any improvement has been observed, has been attributed to the release of trophic factors, possibly promoting endogenous repair mechanisms, reducing cell death and stimulating neurogenesis and angiogenesis. Initial human studies indicate that stem cell therapy may be technically feasible in stroke patients, however, issues still need to be addressed for use in human subjects.
The potential benefit of stem cell therapy after stroke: an update
Vascular Health and Risk Management, 2012
Stroke is a leading cause of death and disability worldwide. Stem cell therapy is an emerging therapeutic modality with evidence of significant benefits in preclinical stroke models. A number of phase I and II clinical trials have now been completed, with several more currently under way. Translation to the bedside, however, remains a long way off, and there are many questions that remain unanswered. This review will summarize the current evidence and ongoing clinical trials worldwide, and explore the challenges to making this a realistic treatment option for the future.
Frontiers in Aging Neuroscience, 2014
Attractive therapeutic strategies to enhance post-stroke recovery of aged brains include methods of cellular therapy that can enhance the endogenous restorative mechanisms of the injured brain. Since stroke afflicts mostly the elderly, it is highly desirable to test the efficacy of cell therapy in the microenvironment of aged brains that is generally refractory to regeneration. In particular, stem cells from the bone marrow allow an autologous transplantation approach that can be translated in the near future to the clinical practice. Such a bone marrow-derived therapy includes the grafting of stem cells as well as the delayed induction of endogenous stem cell mobilization and homing by the stem cell mobilizer granulocyte colony-stimulating factor (G-CSF). We tested the hypothesis that grafting of bone marrow-derived pre-differentiated mesenchymal cells (BM-MSCs) in G-CSF-treated animals improves the long-term functional outcome in aged rodents. To this end, G-CSF alone (50 µg/kg) or in combination with a single dose (10 6 cells) of rat BM MSCs was administered intravenously to Sprague-Dawley rats at 6 h after transient occlusion (90 min) of the middle cerebral artery. Infarct volume was measured by magnetic resonance imaging at 3 and 48 days post-stroke and additionally by immunhistochemistry at day 56. Functional recovery was tested during the entire post-stroke survival period of 56 days. Daily treatment for post-stroke aged rats with G-CSF led to a robust and consistent improvement of neurological function after 28 days. The combination therapy also led to robust angiogenesis in the formerly infarct core and beyond in the "islet of regeneration." However, G-CSF + BM MSCs may not impact at all on the spatial reference-memory task or infarct volume and therefore did not further improve the post-stroke recovery. We suggest that in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time.
Recovery and rehabilitation in stroke Stem cells
The recent demostration that neurons for transplantation can be generated from stem cells and that the adult brain produces new neurons in response to stroke has raised hope for the development of a stem cell therapy for patients affected with this disorder. In this review we propose a road map to the clinic and describe the different scientific tasks that need to be accomplished to move stem cell-based approaches toward application in stroke patients. (Stroke. 2004; 35[suppl I]:2691-2694.)
Stem cell-based therapies for ischemic stroke
BioMed research international, 2014
In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs), inducible pluripotent stem cells (iPSCs), neural stem cells (NSCs), and mesenchymal stem cell (MSCs) might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.