Exosomes/miRNAs as mediating cell-based therapy of stroke

Hongqi Xin, Yi Li, Michael Chopp, Hongqi Xin, Yi Li, Michael Chopp

Abstract

Cell-based therapy, e.g., multipotent mesenchymal stromal cell (MSC) treatment, shows promise for the treatment of various diseases. The strong paracrine capacity of these cells and not their differentiation capacity, is the principal mechanism of therapeutic action. MSCs robustly release exosomes, membrane vesicles (~30-100 nm) originally derived in endosomes as intraluminal vesicles, which contain various molecular constituents including proteins and RNAs from maternal cells. Contained among these constituents, are small non-coding RNA molecules, microRNAs (miRNAs), which play a key role in mediating biological function due to their prominent role in gene regulation. The release as well as the content of the MSC generated exosomes are modified by environmental conditions. Via exosomes, MSCs transfer their therapeutic factors, especially miRNAs, to recipient cells, and therein alter gene expression and thereby promote therapeutic response. The present review focuses on the paracrine mechanism of MSC exosomes, and the regulation and transfer of exosome content, especially the packaging and transfer of miRNAs which enhance tissue repair and functional recovery. Perspectives on the developing role of MSC mediated transfer of exosomes as a therapeutic approach will also be discussed.

Keywords: Exosome; bio-information transfer; cell-based therapy; microRNAs (miRNAs); multipotent mesenchymal stromal cell (MSC); stroke.

Figures

Figure 1
Figure 1
The generation of MSC exosomes and bio-information shuttling between MSCs and brain parenchymal cells via exosomes. Exosomes are generated in the late endosomal compartment by inward budding of the limiting membrane of MVB. The exosome-filled MVBs are either fused with the plasma membrane to release exosomes or sent to lysosomes for degradation. Microvesicles are plasma membrane derived particles that are released into the extracellular environment by the direct outward budding and fission of the plasma membrane. The bio-information carried by MSC exosomes then transfer to brain parenchymal cells like astrocytes and neurons. ILV, intraluminal vesicles; MVB, multivesicular body; GC, Golgi complex; RER, rough endoplasmic reticulum.

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