Abstract
IntroductionPeritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD). Combination therapies are emerging as a promising treatment for tissue damage. Here, we investigated the therapeutic potential of SIRT1-modified human umbilical cord mesenchymal stem cells (hUCMSCs) for peritoneal fibrosis.MethodsSIRT1 was overexpressed in hUCMSCs to establish SIRT1-modified hUCMSCs. Co-culture and transplantation experiments were performed in TGF-β-stimulated Met-5A cells and peritoneal damage rodent model to assess the therapeutic potential of SIRT1-modified hUCMSCs for peritoneal fibrosis through qPCR, Western blot, and peritoneal function analyses.ResultsSIRT1-modified hUCMSC administration had more potent anti-fibrosis ability than hUCMSCs, which significantly inhibited the expression of fibrotic genes and suppressed EMT process, increased ultrafiltration volume, and restored homeostasis of bioincompatible factors in dialysis solution. Mechanistically, SIRT1-modified hUCMSCs attenuated peritoneal fibrosis through reducing peritoneal inflammation and inhibiting the TGF-β/Smad3 pathway in peritoneal omentum tissues.ConclusionSIRT1-modified hUCMSCs might work as a promising therapeutic strategy for the treatment of peritoneal dialysis-induced peritoneal damage and fibrosis.
Highlights
Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD)
Positive and negative surface markers of Mesenchymal stem cells (MSCs) were detected by flow cytometry based on the criteria of MSC identity created by the International Society for Cellular Therapy [26, 28]
The result showed that positive surface markers, CD90 and CD105, are highly expressed on these human umbilical cord mesenchymal stem cells (hUCMSCs), while the negative surface markers, CD34 and CD45, are rarely expressed on the cells (Table 2, control)
Summary
Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis (PD). Combination therapies are emerging as a promising treatment for tissue damage. Among several therapeutic interventions of peritoneal fibrosis, mesenchymal stem cell (MSC) transplantation has been reported to be promising [8,9,10,11]. Recent reports showed that bone marrow-derived MSC transplantation is able to attenuate peritoneal fibrosis and improve peritoneal damage in rat models [16,17,18]. Wang et al injected rat bone marrow-derived MSCs into peritoneal scraping induced rat injury model and found MSCs can attenuate peritoneal injury through decreasing inflammation, repairing mesothelial cells, and reducing fibrosis [16]. A group from Japan reported that co-culture rat MSCs and human peritoneal mesothelial cells in the Transwell system can significantly suppress epithelial-to-mesenchymal transition (EMT), downregulate the expression of fibrotic genes in human cells, and ameliorate experimental peritoneal fibrosis [17]
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