ABSTRACT Mesenchymal stem cell‐derived exosomes (MSC‐exo) can alleviate hypertrophic scar (HS) formation, whereas Schwann cells (SCs) promote HS formation. This study aimed to investigate whether MSC‐exos attenuate HS by modulating SCs and to elucidate the underlying mechanisms. HS and normal skin tissues were obtained from patients. MSCs, SCs, and fibroblasts were isolated from BALB/c mice. SCs and HS mouse models were treated with MSC‐exos. SCs under various treatments were co‐cultured with fibroblasts. mRNA and protein levels were assessed by qRT‐PCR, western blot, immunofluorescence, and immunohistochemical staining. Cell migration, proliferation, and apoptosis were evaluated by wound healing assay, CCK‐8 assay, and TUNEL assay, respectively. HS tissue morphology was examined by Hematoxylin–eosin and Masson staining. The targeting of miR‐29a‐3p towards PDGFRB was validated using a dual‐luciferase reporter assay. In patient HS tissues, downregulated miR‐29a‐3p was negatively correlated with upregulated PDGFRB. MSC‐exo‐delivered miR‐29a‐3p suppressed SCs proliferation and migration, promoted SCs apoptosis, and reduced SCs‐secreted NGF, thereby inhibiting fibroblast migration and myofibroblast transformation. These effects were reversed by miR‐29a‐3p knockdown in MSCs. Furthermore, miR‐29a‐3p targeted and inhibited PDGFRB expression in SCs. Silencing PDGFRB abolished the promoting effects of miR‐29a‐3p inhibition on SCs, which was rescued by the PAK1 activator FTY720. MSC‐exo‐delivered miR‐29a‐3p ameliorates HS by inhibiting SCs proliferation, migration and NGF secretion via the PDGFRB/PAK1 axis to suppress myofibroblast transformation. Beyond the traditional focus on fibroblasts, this reveals an exosome‐SCs‐fibroblast network, providing a novel theoretical basis for HS treatment.
Zang et al. (Fri,) studied this question.