Bone Marrow-Derived Mesenchymal Stem Cells Expressing Thioredoxin 1 Attenuate Bleomycin-Induced Skin Fibrosis and Oxidative Stress in Scleroderma

Abstract

Systemic sclerosis (SSc) is an autoimmune disorder that affects multiple organs. It is characterized by a thickening of the dermis and connective tissue caused by collagen accumulation, and vascular injuries that induce hypoxia. The present study investigated the therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) expressing thioredoxin 1 (Trx-1) in treating SSc-mediated skin disease after transplantation into a bleomycin-induced murine model. Mice with bleomycin-induced SSc were subcutaneously injected with BMSCs or Trx-1-overexpressing BMSCs and exposed to hypoxic conditions for 48 hours. Two weeks later, skin tissue samples were collected to assess fibrosis, oxidative stress, and angiogenesis by western blotting, ELISA, and histologic and immunofluorescence approaches. In vivo experiments showed that Trx-1-overexpressing BMSCs inhibited hypoxia-induced apoptosis and inhibited fibrosis under hypoxic conditions, possibly by downregulating transforming growth factor-β. Trx-1-overexpressing BMSCs also promoted the formation of tubular-like structures by endothelial progenitor cells, indicating that Trx-1 can promote angiogenesis in bleomycin-induced SSc. These results demonstrate that the transplantation of Trx-1-overexpressing BMSCs restored normal skin tissue in a mouse model of bleomycin-induced SSc, highlighting the therapeutic potential of engineered BMSCs for treating SSc.