Abstract
Stroke is a leading cause of morbidity and mortality worldwide, and consists of two types, ischemic and hemorrhagic. Currently, there is no effective treatment to increase the survival rate or improve the quality of life after ischemic and hemorrhagic stroke in the subacute to chronic phases. Therefore, it is necessary to establish therapeutic strategies to facilitate functional recovery in patients with stroke during both phases. Cell-based therapies, using microglia and monocytes/macrophages preconditioned by optimal stimuli and/or any therapies targeting these cells, might be an ideal therapeutic strategy for managing stroke. Microglia and monocytes/macrophages polarize to the classic pro-inflammatory type (M1-like) or alternative protective type (M2-like) by optimal condition. Cell-based therapies using M2-like microglia and monocytes/macrophages might be protective therapeutic strategies against stroke for three reasons. First, M2-like microglia and monocytes/monocytes secrete protective remodeling factors, thus prompting neuronal network recovery via tissue (including neuronal) and vascular remodeling. Second, these cells could migrate to the injured hemisphere through the blood–brain barrier or choroid–plexus. Third, these cells could mitigate the extent of inflammation-induced injuries by suitable timing of therapeutic intervention. Although future translational studies are required, M2-like microglia and monocytes/macrophages therapies are attractive for managing stroke based on their protective functions.
Highlights
Stroke is a leading cause of morbidity and mortality worldwide, and is categorized into two types, ischemic and hemorrhagic
Microglia-like cells have been derived from cultured human embryonic stem (ES) and induced pluripotent stem cells, and a robust and efficient protocol for the rapid production of microglia-like cells was established [121]
Microglia/monocytes from induced pluripotent stem (iPS) cells might be a potential candidate for therapeutic applications in stroke, provided that the tumorigenesis issue in cells derived from iPS cells is resolved
Summary
Stroke is a leading cause of morbidity and mortality worldwide, and is categorized into two types, ischemic and hemorrhagic. The protective M2-like microglia and monocytes/macrophages exert their effect through the secretion of remodeling factors, such as VEGF, BDNF, and matrix metalloproteinase-9 (MMP-9) [23,24,25], in addition to protective cytokines, such as transforming growth factor-β (TGF-β) and IL-10 [26,27], which may facilitate anti-inflammation, axonal outgrowth, and angiogenesis after ischemic [20,21,27,28] and hemorrhagic stroke [22,29,30]. Because M2-like microglia aand mmoonnooccyytteess//mmaaccrroopphhaaggeess sseeccrreettee protecttiivvee remodeling factors after ischemia, incluuddiinngg VVEEGGFF, BDNF, progranulin, and TGF-β [10,24,28,53], they may facilitate axonal outgrowth and angiogenesis after ischemic stroke.
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