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 hyper‑ trophic scar fibroblasts (HSFBs) was detected via reverse transcription‑quantitative PCR. Exosomes derived from miR‑29a‑modified hADSCs were extracted and the influ‑ ence 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 deter‑ mined 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.