Stem Cell- and Cell-Based Therapies for Ischemic Stroke.

Stroke is the second cause of disability worldwide as it is expected to increase its incidence and prevalence. Despite efforts to increase the number of patients eligible for recanalization therapies, a significant proportion of stroke survivors remain permanently disabled. This outcome boosted the search for efficient neurorestorative methods. Stem cells act through multiple pathways: cell replacement, the secretion of growth factors, promoting endogenous reparative pathways, angiogenesis, and the modulation of neuroinflammation. Although neural stem cells are difficult to obtain, pose a series of ethical issues, and require intracerebral delivery, mesenchymal stem cells are less immunogenic, are easy to obtain, and can be transplanted via intravenous, intra-arterial, or intranasal routes. Extracellular vesicles and exosomes have similar actions and are easier to obtain, also allowing for engineering to deliver specific molecules or RNAs and to promote the desired effects. Appropriate timing, dosing, and delivery protocols must be established, and the possibility of tumorigenesis must be settled. Nonetheless, stem cell- and cell-based therapies for stroke have already entered clinical trials. Although safe, the evidence for efficacy is less impressive so far. Hopefully, the STEP guidelines and the SPAN program will improve the success rate. As such, stem cell- and cell-based therapy for ischemic stroke holds great promise.