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Mesenchymal stem cells cultured in serum-free medium ameliorate experimental peritoneal fibrosis

机译:在无血清培养基中培养的间充质干细胞改善实验性腹膜纤维化

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摘要

Abstract Background Mesenchymal stem cells (MSCs) provide potential treatments for peritoneal fibrosis. However, MSCs cultured in media containing serum bring risks of infection and other problems. In this study, we compared the effect of human MSCs in serum-free medium (SF-MSCs) on peritoneal fibrosis with that of MSCs cultured in medium containing 10% fetal bovine serum (10%MSCs). Methods Peritoneal fibrosis was induced by intraperitoneally injecting 0.1% chlorhexidine gluconate (CG). SF-MSCs or 10%MSCs were intraperitoneally administered 30 min after the CG injection. Ten days after the CG and MSC injections, we performed histological analyses and peritoneal equilibrium testing. In the in vitro experiments, we used transforming growth factor (TGF)-β1-stimulated human peritoneal mesothelial cells incubated in conditioned medium from MSCs to examine whether the SF-MSCs showed enhanced ability to produce antifibrotic humoral factors. Results Histological staining showed that the SF-MSCs significantly suppressed CG-induced cell accumulation and thickening compared with that of the 10%MSCs. Additionally, the SF-MSCs significantly inhibited mesenchymal cell expression, extracellular matrix protein deposition and inflammatory cell infiltration. Peritoneal equilibration testing showed that compared with administering 10%MSCs, administering SF-MSCs significantly reduced the functional impairments of the peritoneal membrane. The in vitro experiments showed that although the conditioned medium from MSCs suppressed TGF-β1 signaling, the suppression did not significantly differ between the SF-MSCs and 10%MSCs. Conclusions Serum-free culture conditions can enhance the antifibrotic abilities of MSCs by suppressing inflammation. Administering ex vivo expanded SF-MSCs may be a potential therapy for preventing peritoneal fibrotic progression.
机译:摘要背景间充质干细胞(MSCs)为腹膜纤维化提供潜在的治疗方法。然而,在含有血清的培养基中培养的MSCs带来了感染风险和其他问题。在这项研究中,我们将人体MSCs在无血清培养基(SF-MSCs)中的影响与含有10%胎牛血清(10%MSC)的培养基中的MSCs培养的腹膜纤维化中的腹膜纤维化中的效果。方法通过腹膜内注射0.1%氯己定葡萄糖酸盐(CG)诱导腹膜纤维化。在CG注射后30分钟腹膜内施用SF-MSCs或10%MSC。 CG和MSC注射后十天,我们进行了组织学分析和腹膜平衡测试。在体外实验中,我们使用转化的生长因子(TGF)-β1刺激的人腹膜间皮细胞在来自MSC的条件培养基中培养的人腹腔间皮细胞,检查SF-MSCs是否显示出增强的产生抗纤维间隔因素的能力。结果组织学染色表明,与10%MSCs相比,SF-MSCs显着抑制了CG诱导的细胞积累和增稠。另外,SF-MSCs显着抑制间充质细胞表达,细胞外基质蛋白沉积和炎症细胞浸润。腹膜平衡测试表明,与施用10%MSCs相比,施用SF-MSCs显着降低了腹膜膜的功能损伤。体外实验表明,尽管来自MSCs的调节培养基抑制了TGF-β1信号传导,但SF-MSCs和10%MSCs之间的抑制没有显着差异。结论通过抑制炎症,无血清培养条件可以增强MSCs的抗纤维化能力。施用离体扩增的SF-MSCs可能是预防腹膜纤维化进展的潜在疗法。

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