Analysis of MicroRNA Profile Alterations in Extracellular Vesicles From Mesenchymal Stromal Cells Overexpressing Stem Cell Factor

Abstract

Mesenchymal stem/stromal cells (MSCs) represent a promising tool to treat cardiovascular diseases. One mode of action through which MSCs exert their protective effects is secretion of extracellular vesicles (EVs). Recently, we demonstrated that rat adipose-derived MSC-overexpressing stem cell factor (SCF) can induce endogenous regenerative processes and improve cardiac function. In the present work, we isolated EVs from intact, GFP- or SCF-overexpressing rat MSC and analyzed microarray datasets of their miRNA cargo. We uncovered a total of 95 differentially expressed miRNAs. We did not observe significant differences between EVs from GFP-MSC and SCF-MSC that may indicate intrinsic changes in MSC after viral transduction. About 80 miRNAs were downregulated in EVs from both SCF- or GFP-MSC. We assembled the miRNA-based network and found several nodes of target genes among which Vim Sept3 and Vsnl1 are involved in regulation of cellular migration that is consistent with our previous EVs data. Topological analyses of the network also revealed that among the downregulated miRNA-rno-miRNA-128-3p that regulates plenty of targets is presumably associated with chemokine signaling pathways. Overall, our data suggest that genetic modification of MSC has a great impact on their miRNA composition and provide novel insights into the regulatory networks underlying EV effects.

SEPT3 as a Potential Molecular Target of Triple-Negative Breast Cancer

“… 23 A recent study concluded that SEPT3 might be involved in regulation of cellular migration mediated by extracellular vesicles in mesenchymal stem cells. 24 Taken together, SEPT3 belongs to cytoskeleton proteins that may promote TNBC cell metastasis.…”

The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

“…In a recent model of myocardial dysfunction, rat adipose-derived MSC-overexpressing stem cell factor (SCF) was successfully used to induce endogenous regenerative processes and improve cardiac function. EVs from genetically modified MSCs were isolated, and a total of 95 differentially expressed miRNAs were identified in intact GFP-or SCF-overexpressing rat MSC EVs [145]. Genetic modification of MSCs can greatly impact EV miR composition [145].…”

“…EVs from genetically modified MSCs were isolated, and a total of 95 differentially expressed miRNAs were identified in intact GFP-or SCF-overexpressing rat MSC EVs [145]. Genetic modification of MSCs can greatly impact EV miR composition [145].…”

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases

“…A gain- and loss-of-function study showed that mir-26a is important for the neuroprotective effect of Evs from AT-MSCs in a model of ischemia/reperfusion (Hou et al, 2021 ). A recent study showed that viral transduction of MSCs may impact their miRNA cargo in Evs (Zubkova et al, 2021 ). Priming MSCs with conditioned medium of activated microglia changed the miRNAs of Evs to a more immune-regulatory profile, which resulted in inhibition of microglial and astrocyte activation and better behavioral function (Markoutsa et al, 2022 ).…”