Bone marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice

被引：113

作者：

Wu, Yan ^{[1
,2
,3
,4
]}

Huang, Sha ^{[1
,4
]}

Enhe, Jirigala ^{[5
]}

Ma, Kui ^{[4
]}

Yang, Siming ^{[1
,4
]}

Sun, Tongzhu ^{[4
]}

Fu, Xiaobing ^{[1
,4
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Inst Basic Med Sci, Beijing 100842, Peoples R China

[2] Nankai Univ, Sch Med, Tianjin 300071, Peoples R China

[3] Mudanjiang Med Coll, Heilongjiang Key Lab Antifibrosis Biotherapy, Mudanjiang, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Affiliated Hosp 1, Burns Inst, Beijing 100842, Peoples R China

[5] Inner Mongolia Med Coll, Sch Basic Med Sci, Hohhot, Peoples R China

来源：

INTERNATIONAL WOUND JOURNAL | 2014年 / 11卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Cell therapy; Fibrosis; Mesenchymal stem cell; Skin scar; Wound healing; GLOBAL HEART-FAILURE; COLLAGEN BIOSYNTHESIS; EXTRACELLULAR-MATRIX; SCLEROTIC SKIN; GROWTH-FACTOR; ANIMAL-MODEL; FIBROBLASTS; SCLERODERMA; REPAIR; TRANSPLANTATION;

D O I：

10.1111/iwj.12034

中图分类号：

R75 [皮肤病学与性病学];

学科分类号：

100206 ;

摘要：

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-1 (TGF-1), type I collagen and heat-shock protein 47 (HSP47), with higher expression of matrix metalloproteinases (MMPs)-2, -9 and -13. Further experiments showed that -smooth muscle actin (-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.

引用

页码：701 / 710

页数：10

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