Abstract
Ischemic stroke (IS) is a serious cerebrovascular disease with high morbidity and disability worldwide. Despite the great efforts that have been made, the prognosis of patients with IS remains unsatisfactory. Notably, recent studies indicated that mesenchymal stem cell (MSCs) therapy is becoming a novel research hotspot with large potential in treating multiple human diseases including IS. The current article is aimed at reviewing the progress of MSC treatment on IS. The mechanism of MSCs in the treatment of IS involved with immune regulation, neuroprotection, angiogenesis, and neural circuit reconstruction. In addition, nutritional cytokines, mitochondria, and extracellular vesicles (EVs) may be the main mediators of the therapeutic effect of MSCs. Transplantation of MSCs-derived EVs (MSCs-EVs) affords a better neuroprotective against IS when compared with transplantation of MSCs alone. MSC therapy can prolong the treatment time window of ischemic stroke, and early administration within 7 days after stroke may be the best treatment opportunity. The deliver routine consists of intraventricular, intravascular, intranasal, and intraperitoneal. Furthermore, several methods such as hypoxic preconditioning and gene technology could increase the homing and survival ability of MSCs after transplantation. In addition, MSCs combined with some drugs or physical therapy measures also show better neurological improvement. These data supported the notion that MSC therapy might be a promising therapeutic strategy for IS. And the application of new technology will promote MSC therapy of IS.
Highlights
Stroke is the second leading cause of death in the world after ischemic heart disease [1]
Some studies have shown that inflammation after ischemia can promote the repair of brain tissue and the recovery of neural function in the chronic phase [23], more evidence supports the adverse effects of inflammatory response
Tobin et al compared the efficacy of interferon-γ pretreated mesenchymal stem cell (MSCs) and normal MSCs in middle cerebral artery occlusion (MCAO) model animals and found that there was no significant difference in functional improvement between the two, interferon-γ pretreated MSCs may have more advantages, which reflected in the fact that interferon-γ pretreated MSCs can induce activated microglia to secrete less proinflammatory cytokines and induce oligodendrocyte differentiation and myelination more effectively [39]
Summary
Stroke is the second leading cause of death in the world after ischemic heart disease [1]. Due to acute neurological deficits caused by focal cerebral ischemia, it has brought different degrees of disability burden to a large number of patients. There are few treatment options for ischemic stroke. Intravenous injection of tissue plasminogen activator (t-PA) can recanalize the blocked vessels. This treatment is limited by a short time window (≤ 4.5 hours) and the risk of secondary cerebral hemorrhage [3]. Rehabilitation treatment can only bring limited functional improvement; there are still a large number of patients with permanent disabilities [5]
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