Bone marrow mesenchymal stem cells alleviate the formation of pathological scars in rats.

ABSTRACT

Introduction: Although bone marrow-derived mesenchymal stem cells (BMSCs) have attracted increasing attention because of their pivotal functions in the process of wound healing and fibrosis alleviation, the underlying molecular mechanisms have been poorly understood. Moreover, transforming growth factor beta 1 (TGF-ß1) is positively correlated with scar formation, whereas TGF-ß3 inhibits the pathological scar formation process. However, the relation of TGF-ß1, TGF-ß3, and the TGF-ß/Smad signaling pathway with BMSCs is unknown and requires further investigation. Methods: A cell co-culture platform was used to examine the relationship between BMSCs and dermal fibroblasts (DFs). EdU labelling and cell cycle detection were carried out to examine the viability of DF cells. Transwell and wound healing assays were used to test the cell migration of DFs. The expression of TGF-ß pathway components and collagens were determined by RT-qPCR and western blotting. A damaged skin rat model was applied to test the effects of BMSC treatment on skin wound healing. Results: The results showed that BMSC secretion could inhibit the viability and migration of DFs. Moreover, we observed that the TGF-ß-induced expression of TGF-ß1, Smad2, Smad3, COLI and COLIII was attenuated upon BMSC treatment in DFs, while the decrease in TGF-ß3 expression was enhanced by BMSCs. Furthermore, BMSC treatment accelerated wound healing and attenuated skin collagen deposition in a damaged skin rat model, leading to the mitigation of cell proliferation and enhancement of cell apoptosis. In addition, the expression of alpha-smooth muscle actin (α-SMA), COLI, and COLII was alleviated by BMSC treatment. Conclusions: Our results indicate that BMSCs can promote wound healing and inhibit skin collagen deposition, which is associated with the TGF-ß/Smad signaling pathway.