Abstract
Stem cell therapy is a promising potential therapeutic strategy to treat cerebral ischemia in preclinical and clinical trials. Currently proposed treatments for stroke employing stem cells include the replacement of lost neurons and integration into the existing host circuitry, the release of growth factors to support and promote endogenous repair processes, and the secretion of extracellular vesicles containing proteins, noncoding RNA, or DNA to regulate gene expression in recipient cells and achieve immunomodulation. Progress has been made to elucidate the precise mechanisms underlying stem cell therapy and the homing, migration, distribution, and differentiation of transplanted stem cells in vivo using various imaging modalities. Noninvasive and safe tracer agents with high sensitivity and image resolution must be combined with long-term monitoring using imaging technology to determine the optimal therapy for stroke in terms of administration route, dosage, and timing. This review discusses potential therapeutic mechanisms of stem cell transplantation for the treatment of stroke and the limitations of current therapies. Methods to label transplanted cells and existing imaging systems for stem cell labeling and in vivo tracking will also be discussed.
Highlights
Stroke is a leading cause of death and long-term disability worldwide [1,2,3,4,5], and current epidemiological data suggest that the economic and social burdens of this disease will progressively increase over the few decades
Preclinical data suggest that stem cell therapy is a promising regenerative medical treatment given the limited capacity of the central nervous system (CNS) for self-repairs after ischemic stroke
MiR-133b released from mesenchymal stem cells (MSCs) was transferred into astrocytes and neurons via exosomes both in vitro and in vivo, regulating connective tissue growth factor (CTGF) and ras homolog gene family member A (RhoA) expression and increasing axonal plasticity and neurite remodeling in the ischemic boundary zone (IBZ), subsequently promoting functional recovery after stroke [94, 95]
Summary
Stroke is a leading cause of death and long-term disability worldwide [1,2,3,4,5], and current epidemiological data suggest that the economic and social burdens of this disease will progressively increase over the few decades. Intravenous tPA enhances the risk of cerebral hemorrhage which limits its clinical application [16] In recent year, another promising strategy for treatment of acute ischemic stroke is endovascular blood clot removal in large cerebral arteries with a stent retrieve [17, 18]. Numerous randomized trials have suggested that patients with a proximal cerebral arterial occlusion treated with rapid endovascular treatment could improve reperfusion and functional neurologic outcomes better than systemic tPA [19,20,21]. Preclinical data suggest that stem cell therapy is a promising regenerative medical treatment given the limited capacity of the central nervous system (CNS) for self-repairs after ischemic stroke. The potential therapeutic mechanisms of stem cell transplantation for the treatment of stroke and the limitations of current therapies will be discussed. We will discuss methods for labeling transplanted cells and existing imaging systems for stem cell labeling and tracking in vivo
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