Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6.
Mesenchymal stem cells attenuate peritoneal injury through secretion of TSG-6.
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间充质干细胞通过分泌 TSG-6 减轻腹膜损伤
DOI：
10.1371/journal.pone.0043768
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Wang N;Li Q;Zhang L;Lin H;Hu J;Li D;Shi S;Cui S;Zhou J;Ji J;Wan J;Cai G;Chen X
背景间皮细胞损伤在腹膜纤维化中起重要作用。目前旨在减轻腹膜纤维化的临床治疗在很大程度上是不够的。间充质干细胞（MSC）是修复损伤和减少纤维化的有效方法。本研究旨在探讨骨髓间充质干细胞对损伤的间皮细胞和腹膜纤维化的影响。方法/主要发现大鼠骨髓来源的MSC（5 ×106）在腹膜刮除后24 h经尾静脉注射到Sprague-Dawley（SD）大鼠中。MSC治疗组大鼠的粘附形成、中性粒细胞、巨噬细胞浸润、成纤维细胞数量和转化生长因子（TGF）-β1水平明显减少。MSC处理的大鼠腹膜间皮细胞的增殖和修复受到刺激。机械损伤的间皮细胞与间充质干细胞在transwells中共培养显示出迁移和增殖的明显增加。体内成像显示，静脉注射的MSC主要积聚在肺部，持续至少7天。即使腹腔注射MSCs，在损伤的腹膜中也没有观察到明显的MSCs。静脉注射血清饥饿的MSC条件培养基（CM）减少了与MSC相似的粘连。MSCs-CM蛋白质芯片显示TNFα刺激基因（TSG）-6的释放量增加最明显。重组小鼠TSG-6可促进间皮细胞修复和减少腹膜粘连，但可被TSG-6-RNA干扰所减弱。结论/意义总的来说，这些结果表明MSC可以通过修复间皮细胞，减少炎症和纤维化来减轻腹膜损伤。MSC分泌TSG-6而不是植入对MSC的治疗益处做出了主要贡献。
Background Mesothelial cell injury plays an important role in peritoneal fibrosis. Present clinical therapies aimed at alleviating peritoneal fibrosis have been largely inadequate. Mesenchymal stem cells (MSCs) are efficient for repairing injuries and reducing fibrosis. This study was designed to investigate the effects of MSCs on injured mesothelial cells and peritoneal fibrosis. Methodology/Principal Findings Rat bone marrow-derived MSCs (5 ×106) were injected into Sprague-Dawley (SD) rats via tail vein 24 h after peritoneal scraping. Distinct reductions in adhesion formation; infiltration of neutrophils, macrophage cells; number of fibroblasts; and level of transforming growth factor (TGF)-β1 were found in MSCs-treated rats. The proliferation and repair of peritoneal mesothelial cells in MSCs-treated rats were stimulated. Mechanically injured mesothelial cells co-cultured with MSCs in transwells showed distinct increases in migration and proliferation. In vivo imaging showed that MSCs injected intravenously mainly accumulated in the lungs which persisted for at least seven days. No apparent MSCs were observed in the injured peritoneum even when MSCs were injected intraperitoneally. The injection of serum-starved MSCs-conditioned medium (CM) intravenously reduced adhesions similar to MSCs. Antibody based protein array of MSCs-CM showed that the releasing of TNFα-stimulating gene (TSG)-6 increased most dramatically. Promotion of mesothelial cell repair and reduction of peritoneal adhesion were produced by the administration of recombinant mouse (rm) TSG-6, and were weakened by TSG-6-RNA interfering. Conclusions/Significance Collectively, these results indicate that MSCs may attenuate peritoneal injury by repairing mesothelial cells, reducing inflammation and fibrosis. Rather than the engraftment, the secretion of TSG-6 by MSCs makes a major contribution to the therapeutic benefits of MSCs.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.0508945102
发表时间：
2005-12-13
影响因子：
11.1
作者：
Munoz, JR;Stoutenger, BR;Prockop, DJ
通讯作者：
Prockop, DJ