Exosomes Derived From Mesenchymal Stem Cells: Novel Effects in the Treatment of Ischemic Stroke

Abstract

Ischemic stroke is defined as an infarction in the brain, caused by impaired cerebral blood supply, leading to local brain tissue ischemia, hypoxic necrosis, and corresponding neurological deficits. At present, revascularization strategies in patients with acute ischemic stroke include intravenous thrombolysis and mechanical endovascular treatment. However, due to the short treatment time window (<4.5 h) and method restrictions, clinical research is focused on new methods to treat ischemic stroke. Exosomes are nano-sized biovesicles produced in the endosomal compartment of most eukaryotic cells, containing DNA, complex RNA, and protein (30–150 nm). They are released into surrounding extracellular fluid upon fusion between multivesicular bodies and the plasma membrane. Exosomes have the characteristics of low immunogenicity, good innate stability, high transmission efficiency, and the ability to cross the blood–brain barrier, making them potential therapeutic modalities for the treatment of ischemic stroke. The seed sequence of miRNA secreted by exosomes is base-paired with complementary mRNA to improve the microenvironment of ischemic tissue, thereby regulating downstream signal transduction activities. With exosome research still in the theoretical and experimental stages, this review aims to shed light on the potential of exosomes derived from mesenchymal stem cells in the treatment of ischemic stroke.

Extracellular Vesicles as Delivery Shippers for Noncoding RNA‐Based Modulation of Angiogenesis: Insights from Ischemic Stroke and Cancer

“…Overcoming drug resistance and expanding the clinical application of conventional drugs are also crucial. [ 338 ] Despite insufficient information to translate EV therapy into clinical practice, because only one clinical trial adopting EVs to treat ischemic stroke was reported, [ 339 ] currently, there are 35 clinical trials related to EV‐associated ncRNAs with diverse states, as provided at https://www.clinicaltrials.gov/.…”

Bone marrow mesenchymal stem cell-derived exosomal lncRNA KLF3-AS1 stabilizes Sirt1 protein to improve cerebral ischemia/reperfusion injury via miR-206/USP22 axis

“…Exosomes carry numerous molecules, such as proteins, mRNAs and other RNA species, which are thought to be of paramount importance for intercellular communication (Li et al 2021 ). For treating ischemic stroke, stem cells-secreted exosomes could be a prospective therapeutic choice due to the unique properties, including low immunogenicity and stable biological characteristic (Xiong et al 2022 ). Plenty of researches have also implied that bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) might supply a therapeutic strategy for relieving neuroinflammation after cerebral I/R injury (Liu et al 2021 ).…”

Neuroprotective Effect of Wharton’s Jelly-Derived Mesenchymal Stem Cell-Conditioned Medium (WJMSC-CM) on Diabetes-Associated Cognitive Impairment by Improving Oxidative Stress, Neuroinflammation, and Apoptosis

“…The MSC-CM contains bioactive factors including exosomes and soluble factors such as neurotrophic factors, angiogenic factors, immunosuppressive factors, and other regenerative agents [25][26][27]. Exosomes are extracellular vesicles that can be secreted by various types of mesenchymal stem cells including human umbilical cordderived mesenchymal stem cells [28]. They are one component of MSC-generated conditioned medium (CM) and contain numerous biologically active genomic and nongenomic molecules, including DNA, miRNAs, various proteins, enzymes, and lipids, which can influence the biological activity of cells via paracrine or autocrine pathways.…”

“…They are one component of MSC-generated conditioned medium (CM) and contain numerous biologically active genomic and nongenomic molecules, including DNA, miRNAs, various proteins, enzymes, and lipids, which can influence the biological activity of cells via paracrine or autocrine pathways. It has been indicated that MSC-conditioned medium or its components mediate some biological actions of MSCs [ 27 , 28 ]. Several studies found that these bioactive factors are capable of repairing tissue in a variety of tissue/organ damage conditions [ 26 , 29 ].…”