Open AccessBone marrow‐derived mesenchymal stem cell attenuates skin fibrosis development in mice
Author(s) -
Wu Yan,
Huang Sha,
Enhe Jirigala,
Ma Kui,
Yang Siming,
Sun Tongzhu,
Fu Xiaobing
Publication year - 2014
Publication title -
international wound journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.867
H-Index - 63
eISSN - 1742-481X
pISSN - 1742-4801
DOI - 10.1111/iwj.12034
Subject(s) - mesenchymal stem cell , medicine , myofibroblast , fibrosis , pathology , extracellular matrix , transplantation , bone marrow , wound healing , cancer research , immunology , microbiology and biotechnology , biology
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.