State Key Laboratory of Kidney Diseases, Department of Nephrology, PLA General Hospital and Military Medical Postgraduate College, Beijing, China.
PLoS One. 2012;7(8):e43768. doi: 10.1371/journal.pone.0043768. Epub 2012 Aug 17.
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 × 10(6)) 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.
间皮细胞损伤在腹膜纤维化中起着重要作用。目前旨在缓解腹膜纤维化的临床治疗方法在很大程度上还不够充分。间充质干细胞（MSCs）在修复损伤和减少纤维化方面非常有效。本研究旨在探讨 MSCs 对受损间皮细胞和腹膜纤维化的影响。
方法/主要发现：在腹膜刮除后 24 小时，通过尾静脉向 Sprague-Dawley（SD）大鼠注射 5×10（6）个大鼠骨髓来源的 MSCs。在 MSCs 治疗的大鼠中，发现黏附形成、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水平明显降低。MSCs 治疗的大鼠中，腹膜间皮细胞的增殖和修复受到刺激。在 Transwell 中与 MSCs 共培养的机械损伤的间皮细胞显示出明显的迁移和增殖增加。体内成像显示，静脉内注射的 MSCs 主要积聚在肺部，至少持续七天。即使静脉内注射 MSCs，在受损的腹膜中也没有明显的 MSCs 观察到。静脉内注射血清饥饿的 MSCs 条件培养基（CM）可减少与 MSCs 相似的黏附。MSCs-CM 的基于抗体的蛋白质阵列显示，TNFα刺激基因（TSG）-6 的释放增加最为显著。给予重组小鼠（rm）TSG-6 可促进间皮细胞修复和减少腹膜黏附，而 TSG-6-RNA 干扰则减弱了这种作用。
结论/意义：综上所述，这些结果表明，MSCs 可能通过修复间皮细胞、减少炎症和纤维化来减轻腹膜损伤。MSCs 的分泌而不是植入，对 MSCs 的治疗益处有主要贡献。
