MSC-released TGF-β regulate α-SMA expression of myofibroblast during wound healing.

Abstract

Objective: Wound healing without fibrosis remains a clinical challenge and a new strategy to promote the optimal wound healing is needed. Mesenchymal stem cells (MSCs) can completely regenerate tissue injury due to the robust MSCs ability in controlling inflammation niche leading to granulation tissue formation, particularly through a release of various growth factors including transforming growth factor-β (TGF-β). In response to TGF-β stimulation, fibroblasts differentiate into myofibroblast, marked by alpha-smooth muscle actin (α-SMA) that leads to wound healing acceleration. On the other hand, sustained activation of TGF-β in wound areas may contribute to fibrosis-associated scar formation. The aim of this study was to evaluate the α-SMA expression of myofibroblast induced by MSC-released TGF-β during wound healing process. Materials and Methods: Twenty-four full-thickness excisional rat wound models were randomly divided into four groups: sham (Sh), Control (C), and MSCs treatment groups; topically treated by the MSCs at doses 2x10⁶ cells (T1) and 1x10⁶ cells (T2), respectively. While the control group was treated with NaCl. TGF-β level was determined using ELISA assay, α-SMA expression of myofibroblast was analyzed by immunofluorescence staining, and wound size measurement was calculated using a standard caliper. Results: This study showed a significant increase in TGF-β levels in all treatment groups on days 3 and 6. This finding was consistent with a significant increase of α-SMA expression of myofibroblast at day 6 and wound closure percentage, indicating that MSCs might promote an increase of wound closure. Conclusion: MSCs regulated the release of TGF-β to induce α-SMA expression of myofibroblast for accelerating an optimal wound healing.