Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery

Abstract

Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.

Progress in Mesenchymal Stem Cell Therapy for Ischemic Stroke

“…Secondly, the risk of vascular occlusion and microvascular thrombosis is reduced after transplantation, and MSC-EVs do not have the potential of tumor transformation because they cannot self-replicate. Third, MSC-EV has a robust structure and can be stored at -80°for a long time without loss of biological activity [198]. Finally, intravenous injection of MSC-EVs can reduce the peripheral immunosuppression (i.e., the decrease of B cells, NK cells, and T cells) after IS [95].…”

Safety of intraparenchymal injection of allogenic placenta mesenchymal stem cells derived exosome in patients undergoing decompressive craniectomy following malignant middle cerebral artery infarct, a pilot randomized clinical trial

“…Activation of CD4 and CD6 T lymphocytes and the decrease of the decline in dendritic cells can be intensified by MSC exosomes. [ 23 ] In animal studies, the increase in oligodendrogenesis-associated markers (2′, 3′-cyclic-nucleotide 3′-phosphodiesterase [CNPase], A2B5, and myelin oligodendrocyte glycoprotein) are associated with the white matter repair. [ 24 25 ]…”

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

“…However, diabetes mellitus leads to vascular endothelial cell dysfunction and exuberant angiogenesis, but it is also conducive to dysfunctional neovascularization and poor recovery in ischemic stroke. EPCs can contribute to vascular endothelial repair and angiogenesis ( 34 ); increasing angiogenesis is associated with neurological functional outcome after stroke ( 35 ). Our in vivo study indicated that LV-APN-EPCs treatment had effects on the recovery of neurological functional deficits in diabetic stroke rats, but EPC transplantation alone had little effect.…”