title: Bone marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice.
abstract: Recent studies showed that mesenchymal stem cell (MSC) transplantation significantly alleviated tissue fibrosis; however, little is known about the efficacy on attenuating cutaneous scar formation. In this study, we established a dermal fibrosis model induced by bleomycin and evaluated the benefit of bone marrow-derived mesenchymal stem cells (BM-MSCs) on skin fibrosis development. Tracing assay of green fluorescent protein (GFP(+) )BM-MSCs showed that the cells disappeared gradually within 24 hours upon administration, which hinted the action of BM-MSCs in vivo was exerted in the initial phase of repair in this model. Therefore, we repeatedly transplanted syngeneic BM-MSCs in the process of skin fibrosis formation. After 3 weeks, it was found that BM-MSC-treated lesional skin demonstrated a unanimous basket-weave organisation of collagen arrangement similar to normal skin, with few inflammatory cells. In addition, lesional skin with BM-MSC treatment exhibited a significant down-regulation of transforming growth factor-β1 (TGF-β1), type I collagen and heat-shock protein 47 (HSP47), with higher expression of matrix metalloproteinases (MMPs)-2, -9 and -13. Further experiments showed that α-smooth muscle actin (α-SMA) positive cells, the most reliable marker of myofibroblasts, apparently decreased after BM-MSC transplantation, which revealed that BM-MSCs could attenuate myofibroblast proliferation and differentiation as well as matrix production. Taken together, these findings suggested that BM-MSCs can inhibit the formation process of bleomycin-induced skin fibrosis, alleviate inflammation and favour the remodelling of extracellular matrix.
authors: The Institute of Basic Medical Sciences, Chinese PLA General Hospital, Beijing, China; School of Medicine, Nankai University, Tianjin, China; Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical College, Mudanjiang, China; Burns Institute, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, China.
authors: Yan
authors: Y
authors: Wu
authors: Sha
authors: S
authors: Huang
authors: Jirigala
authors: J
authors: Enhe
authors: Kui
authors: K
authors: Ma
authors: Siming
authors: S
authors: Yang
authors: Tongzhu
authors: T
authors: Sun
authors: Xiaobing
authors: X
authors: Fu
mesh_terms: D000818:Animals; D001761:Bleomycin; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D053505:Matrix Metalloproteinases, Secreted
keywords: Cell therapy; Fibrosis; Mesenchymal stem cell; Skin scar; Wound healing