Peritoneal fibrosis (PF) represents a long-term complication of peritoneal dialysis (PD), affecting the peritoneal membrane (PM) function. Adipose tissue-derived mesenchymal stem cells (ASC) display immunomodulatory effects and may represent a strategy to block PF. The aim of this study was to analyze the effect of ASC in an experimental PF model developed in uremic rats. To mimic the clinical situation of patients on long-term PD, a combo model, characterized by the combination of PF and chronic kidney disease (CKD), was developed in Wistar rats. Rats were fed with a 0.75% adenine-containing diet, for 30 days, to induce CKD with uremia. PF was induced with intraperitoneal injections of chlorhexidine gluconate (CG) from day 15 to 30. ASC were intravenously injected at days 15 and 21. Rats were divided into 5 groups: control, normal rats; CKD, rats receiving adenine diet; PF, rats receiving CG; CKD+PF, CKD rats with PF; CKD+PF+ASC, uremic rats with PF treated with ASC. PF was assessed by Masson trichrome staining. Inflammation- and fibrosis-associated factors were assessed by immunohistochemistry, multiplex analysis, and qPCR. When compared with the control and CKD groups, GC administration induced a striking increase in PM thickness and inflammation in the PF and CKD+PF groups. The development of PF was blocked by ASC treatment. Further, the upregulation of profibrotic factors (TGF-β, fibronectin, and collagen) and the increased myofibroblast expression observed in the CKD+PF group were significantly ameliorated by ASC. Beyond the antifibrotic effect, ASC showed an anti-inflammatory effect avoiding leucocyte infiltration and the overexpression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) in the PM induced by GC. ASC were effective in preventing the development of PF in the experimental model of CKD+PF, probably due to their immunomodulatory properties. These results suggest that ASC may represent a potential strategy for treating long-term PD-associated fibrosis.

中文翻译：

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脂肪来源的间充质干细胞调节尿毒症大鼠腹膜纤维化模型中的纤维化和炎症。

腹膜纤维化（PF）代表腹膜透析（PD）的长期并发症，影响腹膜（PM）的功能。源自脂肪组织的间充质干细胞（ASC）具有免疫调节作用，可能代表了阻断PF的策略。这项研究的目的是分析ASC在尿毒症大鼠实验PF模型中的作用。为了模拟长期PD的患者的临床情况，在Wistar大鼠中开发了一种以PF和慢性肾脏病（CKD）相结合为特征的组合模型。给大鼠喂食0.75％含腺嘌呤的饮食，持续30天，以诱导尿毒症引起的CKD。从第15天到30天腹腔注射葡萄糖酸氯己定（CG）诱导PF。在第15天和第21天静脉内注射ASC。将大鼠分为5组：对照组，正常大鼠；和对照组。CKD，接受腺嘌呤饮食的大鼠；PF，接受CG的大鼠；CKD + PF，CKD大鼠伴PF；CKD + PF + ASC，尿毒症大鼠，ASC处理的PF。通过Masson三色染色评估PF。通过免疫组织化学，多元分析和qPCR评估炎症和纤维化相关因子。与对照组和CKD组相比，GC给药导致PF和CKD + PF组的PM厚度和炎症显着增加。PF的发展被ASC治疗所阻断。此外，纤维化因子（TGF- β，纤连蛋白和胶原蛋白）以及在CKD + PF组中观察到的成肌纤维细胞表达的增加均被ASC改善。除抗纤维化作用外，ASC还显示出抗炎作用，可避免白细胞浸润和GC诱导的PM中炎症细胞因子（IL- 1β，TNF - α和IL-6）的过表达。在CKD + PF实验模型中，ASC可以有效地预防PF的发展，这可能是由于它们的免疫调节特性。这些结果表明，ASC可能代表一种治疗长期PD相关纤维化的潜在策略。