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

Abstract

Mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) have emerged as innovative therapeutic agents for the treatment of sepsis and acute respiratory distress syndrome (ARDS). Although their potential remains undisputed in pre-clinical models, this has yet to be translated to the clinic. In this review, we focused on the role of microRNAs contained in MSC-derived EVs, the EV microRNAome, and their potential contribution to therapeutic mechanisms of action. The evidence that miRNA transfer in MSC-derived EVs has a role in the overall therapeutic effects is compelling. However, several questions remain regarding how to reconcile the stochiometric issue of the low copy numbers of the miRNAs present in the EV particles, how different miRNAs delivered simultaneously interact with their targets within recipient cells, and the best miRNA or combination of miRNAs to use as therapy, potency markers, and biomarkers of efficacy in the clinic. Here, we offer a molecular genetics and systems biology perspective on the function of EV microRNAs, their contribution to mechanisms of action, and their therapeutic potential.

Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design

“…They have been primarily ascribed to exosomal miRNA. Their prominence in regulating physiological responses and their therapeutic relevance have recently led Dos Santos et al to term them an MSC-EV-miRNAome [ 214 ]. When transported in MSC-derived exosomes, miRNAs are potent elicitors of biological responses, exerting immunomodulatory responses and anti-apoptotic or anti-proliferative actions.…”

Laboratory Tools to Predict CFTR Modulator Therapy Effectiveness and to Monitor Disease Severity in Cystic Fibrosis

“…In recent years, EVs have been intensively investigated not only as potential treatments [123,124] but also as suitable sources of biomarkers for assessing disease states [125]. These consist of lipid-membrane-bound vesicles that range between 0.03 and 5.0 µm in diameter and contain bioactive cargoes, including proteins, lipids, DNA, mRNAs, and microR-NAs, among others; these reflect the physiologic or pathologic state of parental cells [125].…”