Aging-related changes of miR-23b-3p expression in extracellular vesicles from mesenchymal stromal cells affect TGFBR3 signaling.

Extracellular vesicles (EVs), which carry biological mediators such as microRNAs (miRNAs) and cytokines, play a crucial role in regulating recipient tissues and are considered a key mechanism of action in cell therapy. However, it has been found that cellular aging in donor cells significantly affects the expression profiles of these mediators involved in intercellular communication. In this study, we identified miR-23b-3p as a regulator of stemness-associated genes through its targeting of TGFBR3, with its expression differing between mesenchymal stem cells (MSCs) from young and aged donors. In aged MSCs, hypermethylation of the human MIR23B promoter region led to its downregulation. Treatment with the demethylating agent valproic acid restored miR-23b-3p expression and facilitated its incorporation into EVs. Our findings indicate that aging in MSCs alters the miRNA composition of EVs, potentially disrupting intercellular communication and significantly impacting the therapeutic efficacy of cell transplantation. To address this issue, the induction of demethylation may represent a promising strategy to improve treatment outcomes of MSCs.