![]() 1).įor stem cell therapy to be useful in augmenting the recovery after stroke, it needs to be safe and effective, applicable to a broad spectrum of patients with stroke, and cost-effective. 16 Thus, MSCs are thought to play multiple roles ( Fig. 14 15 However, it was also reported that subpopulations of MSCs (e.g., multilineage differentiating stress-enduring cells) were able to differentiate into neuronal cells, and were integrated into the peri-infarcted cortex and acted as tissue repair cells. Preclinical studies have found that most injected stem cells disappear within a few weeks, which makes it unlikely that the transplanted stem cells were functionally integrated into the brain. 8 In addition, MSCs exert their actions by attenuating inflammation, 9 10 reducting scar thickness (which may interfere with the recovery process), 11 enhancing autophagy, 12 and normalizing microenvironmental/metabolic profiles 13 in various brain diseases. 4 5 6 7 Besides trophic factors, MSCs release extra-cellular vesicles to deliver functional proteins and microRNAs to NSCs or neuronal cells. The above-described features mean that adult stem cells such as MSCs may be a good choice for stroke therapy because they secrete a variety of bioactive substances-including trophic factors-into the injured brain, which may be associated with enhanced neurogenesis, angiogenesis, and synaptogenesis. True neuronal substitution requires specific anatomic and functional profiles, such as the need for biode-gradable scaffolds (longitudinal channel-like structures for axonal connections) and topologic transplantation of different types of stem-cell-derived neurons (cortical neurons, interneurons, and oligodendrocytes). 2 In addition, there are hurdles associated with using cell replacement to restore neuronal function after stroke. A recent study found that although iPSC-derived NSCs induced neurogenesis, they enhanced endogenous neurogenesis via trophic support, in a manner similar to adult nonneuronal stem cells (e.g., MSCs), rather than by cell replacement with exogenous iPSC-derived NSCs. Most preclinical studies of stem cell therapy for stroke have emphasized the need to enhance self-repair systems rather than to replace lost cells, regardless of the type of cells used (MSC 1 and iPSC 2). Transplanted ESCs, iPSCs, and NSCs can replace the missing brain cells in the infarcted area, while nonneuronal adult stem cells, such as MSCs and MNCs, provide trophic support to enhance self-repair systems such as endogenous neurogenesis. ![]() Stem cells aid stroke recovery via various mechanisms of action depending on the specific cell type used. Sufficient numbers of MSCs can be easily obtained within several weeks of culture expansion. MSCs can migrate to injured brain regions (tropism) and self-renew, reportedly without inducing carcinogenesis. The International Cellular Medicine Society classifies culture-expanded autologous MSCs as a clinical cell line, unlike ESCs, iPSCs, and genetically modified stem cells. Most clinical trials involving patients with stroke have used adult stem cells, such as MSCs, MNCs, and NSCs. 1 Various cell types have been used to improve function and the recovery after stroke, including embryonic stem cells (ESCs), immortalized pluripotent stem cells (iPSCs), neural stem/progenitor cells (NSCs), and nonneuronal adult stem cells such as mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (MNCs). Studies involving animal models of ischemic stroke have shown that stem cells transplanted into the brain can lead to functional improvement. Stem cell therapy is an emerging paradigm in the field of stroke treatment, and is considered a potential regenerative strategy for patients with neurologic deficits. ![]() Stroke is one of the leading causes of death and physical disability among adults, with one-quarter to half of stroke survivors being left with complete or partial dependence on others. ![]()
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