Abstract: Peritoneal fibrosis (PF) is a critical complication of prolonged peritoneal dialysis (PD), driven by epithelial-mesenchymal transition (EMT), oxidative stress, and extracellular matrix accumulation. Current treatments focus on delaying damage rather than reversing fibrosis, highlighting the need for regenerative therapies. Mesenchymal stem cells (MSCs) have shown promise in preclinical models; however, clinical application is limited by challenges in cell harvesting. This study investigates mesenchymal stem cell-like cells derived from peritoneal dialysate (PD-MSC) as a novel, autologous, and clinically accessible cell source for mitigating PF. PD-MSCs were isolated from the dialysate of early-stage PD patients and characterized for MSC markers (positive: CD29, CD44, CD73, CD90, CD105, CD166; negative: CD34, CD79a, HLA-DR) using real-time PCR and FACS analysis. Their differentiation potential into adipocytes, chondrocytes, and osteocytes was assessed. The therapeutic effects of PD-MSCs on TGFβ-induced EMT in peritoneal mesothelial cells (HPMC) were evaluated by real-time PCR, Western blotting, and reactive oxygen species (ROS) assays (DCF-DA and MitoSOX). Anti-fibrotic protein expressions (HGF and BMP-7) were also measured. PD-MSCs expressed characteristic MSC markers and demonstrated trilineage differentiation potential. Treatment with PD-MSCs significantly alleviated transforming growth factor-β-induced EMT in HPMC by restoring epithelial markers and suppressing mesenchymal markers. PD-MSCs also reduced ROS production, as detected by DCF-DA and MitoSOX assays, and restored the expression of HGF and BMP-7, which were downregulated by TGFβ. Compared to T-MSCs, PD-MSCs exhibited comparable or superior efficacy in mitigating EMT, reducing oxidative stress, and promoting anti-fibrotic protein recovery. PD-MSCs derived from early-stage PD patients represent a unique, autologous, and clinically accessible cell source with significant potential for treating peritoneal fibrosis. By alleviating EMT, reducing oxidative stress, and restoring anti-fibrotic factors, PD-MSCs offer a promising therapeutic strategy for preserving peritoneal membrane function in PD patients.
Funding Source: This work was supported by the Korean Fund for Regenerative Medicine (KFRM, 23A0201L1) grant funded by the Korea government (MIST).
Clinical Trial ID number: IRB No. 2019-10-014 in KOREA.
