Mesenchymal Stem Cell-Derived Exosome miR-153-3 Induced M2-Type Polarization of Macrophages to Improve the Healing Effect of Burn Wounds.

Abstract

The healing process of wounds, as soft tissue injuries, is challenging. Bone marrow mesenchymal stem cells (BMSCs) and exosomes (Ex) they secrete are critical for skin wound healing. Paracrine signaling mechanisms appear to facilitate the therapeutic properties of BMSCs. However, BMSC therapy has not yet been extensively explored in terms of specific cellular interactions between macrophages and BMSCs. In this study, macrophage depletion had a substantial negative impact on the wound healing capabilities of BMSCs, highlighting macrophages' crucial role in facilitating wound healing processes mediated by BMSCs. BMSCs transferred to the wound site promoted M2 polarization and alleviated wound healing. The co-cultivation of BMSCs and macrophages resulted in an enhanced phenotypic polarization towards M2. A mechanistic explanation for this effect was found in BMSCs-Ex. Additionally, miR-153-3p, derived from BMSCs-Ex, was identified as a regulator of macrophage polarization via its targeting of KPNA5. Through the transfer of BMSCs-Ex-derived miR-153-3p, BMSCs are capable of promoting M2 polarization and can potentially facilitate wound healing.