Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-β2/Smad3 signaling.

Abstract

Pathological scars mainly refer to hypertrophic scars and keloids, and have a high incidence. Moreover, these scars seriously affect the patient's appearance and are associated with significant pain. The present study aimed to investigate the inhibitory effect of microRNA (miR)-29a from human adipose-derived mesenchymal stem cells (hADSCs) exosomes on scar formation. Firstly, the expression of miR-29a in thermal skin tissues of mice and human hypertrophic scar fibroblasts (HSFBs) was detected via reverse transcription-quantitative PCR. Exosomes derived from miR-29a-modified hADSCs were extracted and the influence of miR-29a-modified hADSCs-exo on the proliferation and function of HSFBs was determined. Lastly, the effect of miR-29a-modified hADSCs-exo on scar formation was determined using a thermal mouse model. The results demonstrated that miR-29a was downregulated in scar tissues after scalding and in HSFBs. After treating HSFBs with miR-29a-modified hADSC exosomes, miR-29a-overexpressing hADSC exosomes inhibited the proliferation and migration of HSFBs. Moreover, it was found that TGF-β2 was the target of miR-29a, and that hADSC exosome-derived miR-29a inhibited the fibrosis of HSFBs and scar hyperplasia after scalding in mice by targeting the TGF-β2/Smad3 signaling pathway. In summary, the current data indicated that miR-29a-modified hADSC exosome therapy can decrease scar formation by inhibiting the TGF-β2/Smad3 signaling pathway via its derived exogenous miR-29a, and this may be useful for the future treatment of pathological scars by providing a potential molecular basis.