Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?


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Abstract

Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF + BM-MSC or G-CSF + BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains. Conclusion: While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time.HighlightsThe aged rat brain microenvironment is not necessarily refractory to cell survival and may also support angiogenesisIt is not clear if the transplanted cells have any beneficial effect on behavioral recoveryThe efficacy of cell therapy can be enhanced by physical rehabilitationThere remain significant developmental and translational issues that remain to be resolved

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