Deciphering the Immunomodulatory Pathways of Mesenchymal Stem Cells

Abstract: Mesenchymal stem cells (MSCs) are adult stem cells with immunoregulatory abilities and low immunogenicity, exhibiting powerful immunosuppressive effects in various inflammatory diseases and holding promise for therapeutic applications. However, the detailed underlying mechanisms remain unclear. Multiple studies suggest that the immunomodulatory function of MSCs is primarily based on the release of immunoregulatory factors through paracrine effects, contributing to their therapeutic outcomes. Other studies report that the immunosuppressive effects of MSCs are mainly achieved through apoptosis, mitochondrial transfer, and the newly proposed migrasomes, highlighting their potential clinical implications. We propose a novel hypothesis, suggesting that migrasomes released by MSCs play a pivotal role in their immunomodulatory ability, potentially offering new avenues for therapeutic interventions. This article primarily summarizes the possible mechanisms by which MSCs exert their immunomodulatory effects, focusing on MSC apoptosis, mitochondrial transfer, and migrasomes, with implications for developing novel therapeutic strategies.