Mesenchymal stem cell-based therapy for ischemic stroke

Abstract

Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

Neuroprotective and neurorestorative actions of mesenchymal stromal cell-derived small extracellular vesicles in the ischemic brain

“…Based on these promising preclinical data, multiple clinical trials of MSCs as a therapy for ischemic stroke have been registered (Table 1). The mechanism of action (MoA) of MSC in ischemic stroke was-as in many other diseases-at first assumed to be cell replacement [74]. Due to the observation that infusion of MSC-derived conditioned medium likewise improved disease outcomes in various settings, a paracrine MoA was discussed quickly [75].…”

Combination therapy for ischemic stroke: Novel approaches to lengthen therapeutic window of tissue plasminogen activator

“…[ 54 ] In addition, significant mitigation of adverse effects associated with delayed tPA treatment was observed when mice were administered minocycline and intracranially transplanted hNSCs 24 h poststroke. [ 54 55 ] This combination therapy suggests tPA, minocycline with stem cell transplantation could attenuate delayed tPA adverse effects as well as induce neuroplasticity following stroke.…”

“…Mesenchymal stem cells (MSCs) have been demonstrated to improve functional outcomes, lower stroke volume, and HT incidence in rats following tPA treatment 1 h and 30 min after reperfusion. [ 28 55 ] The conjunctive treatment also led to diminished MMP-9 levels when compared to the tPA treatment alone. [ 56 ] The ability of MSCs to mitigate endothelial damage is suggested to be the mechanism chiefly responsible for its ability to reduce HT incidence and promote functional recovery.…”

Adjunctive Therapy Approaches for Ischemic Stroke: Innovations to Expand Time Window of Treatment

“…Other types of stem cells have also been investigated and have shown promise in mitigating the complications associated with tPA treatment. Mesenchymal stem cells (MSCs) which have been shown to reduce stroke volume and behavioral deficits in stroke models (for review, [ 55 ]), also reduced incidence of hemorrhage and improved behavioral dysfunctions in rats subjected to tPA (1 h 30 min post stroke, after reperfusion) treatment [ 56 ]. The treatment also reduced MMP-9 levels in the combination tPA + MSC group, compared with tPA alone-treated subjects [ 56 ].…”