Adipose-derived mesenchymal stem cells transplantation facilitate experimental peritoneal fibrosis repair by suppressing epithelial–mesenchymal transition

• Published in: Journal of nephrology 2014-10, Vol.27 (5), p.507-514
• Main Authors: Wakabayashi, Keiichi, Hamada, Chieko, Kanda, Reo, Nakano, Takanori, Io, Hiroaki, Horikoshi, Satoshi, Tomino, Yasuhiko
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Cells, Cultured; Chlorhexidine - analogs & derivatives; Disease Models, Animal; Epithelial-Mesenchymal Transition; Gene Expression Regulation; Injections, Intraperitoneal; Male; Medicine; Medicine & Public Health; Mesenchymal Stem Cell Transplantation; Neovascularization, Physiologic; Nephrology; Original Article; Peritoneal Fibrosis - chemically induced; Peritoneal Fibrosis - genetics; Peritoneal Fibrosis - metabolism; Peritoneal Fibrosis - pathology; Peritoneal Fibrosis - surgery; Peritoneum - metabolism; Peritoneum - pathology; Rats, Sprague-Dawley; Rats, Transgenic; RNA, Messenger - metabolism; Subcutaneous Fat - cytology; Time Factors; Urology
• ISSN: 1121-8428; 1724-6059
• DOI: 10.1007/s40620-014-0133-5

Background Prevention or reversal of peritoneal damage is critical in peritoneal dialysis. Although autologous cell transplantation has beneficial effects on tissue repair in various organs, few studies have investigated the effects of transplantation of adipose-derived mesenchymal stem cells (ASCs) on peritoneal fibrosis (PF). Thus, we examined the mechanism of facilitated peritoneal reconstruction induced by ASC transplantation on chlorhexidine gluconate (CG)-induced PF in rats. Methods To induce PF in rats, continuous-infusion pumps containing 8 % CG were placed in the abdominal cavity for 21 days. The pumps were removed on day 22 and ASCs were immediately injected into the peritoneal cavity. Morphological alterations and mRNA expression levels of fibrosis-related factors were examined on days 29 and 35. Results ASC transplantation significantly facilitated peritoneal repair. mRNA expression of tumor necrosis factor-α, interleukin-1β, monocyte chemotactic protein-1, and epithelial–mesenchymal transition (EMT) markers such as Snail and α-smooth muscle actin were suppressed, whereas that of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB) were overexpressed after ASC transplantation. Immunofluorescence indicated that some transplanted ASCs expressed VEGF and PDGF-BB and differentiated into vascular cells. Conclusions ASC transplantation facilitates peritoneal repair by suppressing EMT and modulating inflammation and angiogenesis during the early phase of tissue repair in experimental PF.