Exosomes from miR-21-5p-modified adipose-derived stem cells promote wound healing by regulating M2 macrophage polarization in a rodent model of pressure ulcer

Abstract

Pressure ulcers represent a significant healthcare burden worldwide. Numerous research has demonstrated the therapeutic potential of adipose-derived stem cell (ADSC)-derived exosomes in promoting wound healing. This study aims to investigate whether exosomes derived from miRNA-modified ADSCs play a role in pressure ulcers by affecting inflammation and macrophage polarization. ADSCs were identified by detecting the surface markers and multilineage differentiation potential. Lentiviruses carrying miR-21-5p were transduced in ADSCs for stable overexpression. Exosomes were extracted from ADSCs and identified. RT-qPCR was employed to detect RNA levels. A mouse model of pressure ulcers was established, followed by injection of exosomes. DiO staining was conducted to assess exosome biodistribution at wound sites. Hematoxylin-eosin and Masson staining were conducted for histological analysis. Immunofluorescence staining was used to evaluate TNF-α and IL-6 expression in mouse wound tissues. Western blotting was conducted to evaluate protein levels of macrophage polarization markers in vivo and in vitro. The results revealed that exosomes derived from miR-21-5p-overexpressing ADSCs promoted wound healing and reduced inflammatory cytokine expression in mouse wound tissues. Moreover, exosomal miR-21-5p induced macrophage M2 polarization in both mouse wound tissues and bone marrow-derived macrophages. Mechanistically, exosomal miR-21-5p inhibited NF-κB signal transduction in mouse wound tissues. In conclusion, ADSC-derived exosomes promote M2 macrophage polarization and inhibit inflammatory response in pressure ulcers via miR-21-5p delivery.