Stem Cell Transplants in the Aged Stroke Brain: Microenvironment Factors

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Popa-Wagner, Aurel
Napoli, Mario Di
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Lapchak, Paul A

Zhang, John H

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2018
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Abstract

In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. The incidence of stroke increases significantly with age both in men and women with incidence rates accelerating above 70 years. Since stroke afflicts mostly the elderly comorbid patients it is highly desirable to test the efficacy of cell therapies in an appropriate animal stroke model. It has been noted that the potential for neurogenesis is also preserved in aged, stroke-injured brains and the environment of the aged brain is not hostile to cell therapies. However, there remain significant developmental and translational issues that remain to be resolved in future studies such as (1) Understanding the differentiation into specific phenotypes. Upon transplantation, the differentiated cells often de-differentiate; (2) Tumorigenesis remains a significant concern; (3) Anti-neuroinflammatory therapies is a potential target to promote regeneration and repair after brain injury and neurodegenerative conditions by stem cell therapy; (4) Efficacy of cell therapy can be enhanced by physical rehabilitation; (5) One potential weakness of the preclinical dataset is, however, the lack of proof in aged subjects. It is in fact a general drawback of preclinical evaluations of candidate stroke drugs that due to cost effectiveness and practicability most studies were done in young animals. A lack of data from aged subjects in preclinical studies may at least in part explain the failure of candidate neuroprotective drugs in clinical trials. The aged brain has compared to the young brain, an enhanced susceptibility to stroke and displays a limited recovery from an ischemic injury. Finally, a better understanding of potential risks of stem cell therapies in stroke shall make the translation of cell therapies safer. Likewise, awareness of may help improve their efficacy to achieve therapeutic success.

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Cellular and Molecular Approaches to Regeneration and Repair

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Biomedical and clinical sciences

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