Extracellular vesicles in mesenchymal stromal cells: A novel therapeutic strategy for stroke (Review)

Abstract

A stroke is a focal cerebral insult that frequently causes severe neurological deficit and mortality. Recent studies have demonstrated that multipotent mesenchymal stromal cells (MSCs) hold great promise for neurovascular remodeling and neurological function recovery following a stroke. Rather than a direct replacement of parenchymal brain cells, the therapeutic mechanism of MSCs is suggested to be the secretion of soluble factors. Specifically, emerging data described MSCs as being able to release extracellular vesicles (EVs), which contain a variety of cargo including proteins, lipids, DNA and various RNA species. The released EVs can target neurocytes and vascular cells and modify the cell's functions by delivering the cargo, which are considered to mediate the neural restoration effects of MSCs. Therefore, EVs may be developed as a novel cell-free therapy for neurological disorders. In the present review, the current advances regarding the components, functions and therapeutic potential of EVs are summarized and the use of MSC-derived EVs as a promising approach in the treatment of stroke are highlighted.

Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy

“…The most common EV markers are ALG-2-interacting protein X (Alix), tetraspanin proteins CD9, CD63, CD81 and heat-shock protein (Hsp)60, Hsp70, and Hsp90. In addition, MSC-released EVs express unique surface antigens including CD44, CD73, CD90 and CD105 [263].…”

“…They overcome some limitations of MSC-based therapies including allogeneic immune rejection, malignant transformation, and premature cell differentiation. EVs have the unique capability to cross the blood-brain barrier, which is very important in the treatment of neurological disorders [263]. This means that EVs have better advantages in the clinic in the treatment of nervous system diseases as compared to the therapeutic potential of MSCs.…”

The potential of exosomes as theragnostics in various clinical situations

“…Recent studies have demonstrated that multipotent mesenchymal stromal cells (MSCs) hold great promise for neurovascular remodeling and neurological function recovery following a stroke. It has been demonstrated that MSC-derived exosomes have a neuroprotective effect against stroke due in part to changing the miRNA profile of exosomes during and after stroke (see [120]).…”

Part Two: Extracellular Vesicles as a Risk Factor in Neurodegenerative Diseases

“…Because of their β1 and α2b integrin-enriched content, human neural stem cell-derived EV administration recovers both tissue and sensorimotor function and may protect the BBB integrity, in the preclinical mouse thromboembolic model of stroke [122,123]. Similarly, multipotent mesenchymal stromal cells (MSCs), through their capacity to secrete soluble factors, play an important role in brain repair.…”

“…Similarly, multipotent mesenchymal stromal cells (MSCs), through their capacity to secrete soluble factors, play an important role in brain repair. It was demonstrated that MSC cargos modulate cell signaling in ischemic stroke by PI3K/Akt pathway activation [123,124] and EVs facilitated secretion of miRs sustaining MSC neuroprotective effects in ischemic stroke as well. Previous research demonstrated that intravenous administration of bone marrow-MSCs containing exosomes transferred miR-133b to astrocytes and neurons into the ischemic boundary zone [120,123], and MSCs cultured in the presence of extracts from rat ischemic brain induced increased expression of exosomal miR133b [123,125].…”