title: The Therapeutic Potential of Human Umbilical Mesenchymal Stem Cells From Wharton's Jelly in the Treatment of Rat Peritoneal Dialysis-Induced Fibrosis.
abstract: A major complication in continuous, ambulatory peritoneal dialysis in patients with end-stage renal disease who are undergoing long-term peritoneal dialysis (PD) is peritoneal fibrosis, which can result in peritoneal structural changes and functional ultrafiltration failure. Human umbilical mesenchymal stem cells (HUMSCs) in Wharton's jelly possess stem cell properties and are easily obtained and processed. This study focuses on the effects of HUMSCs on peritoneal fibrosis in in vitro and in vivo experiments. After 24-hour treatment with mixture of Dulbecco's modified Eagle's medium and PD solution at a 1:3 ratio, primary human peritoneal mesothelial cells became susceptible to PD-induced cell death. Such cytotoxic effects were prevented by coculturing with primary HUMSCs. In a rat model, intraperitoneal injections of 20 mM methylglyoxal (MGO) in PD solution for 3 weeks (the PD/MGO 3W group) markedly induced abdominal cocoon formation, peritoneal thickening, and collagen accumulation. Immunohistochemical analyses indicated neoangiogenesis and significant increase in the numbers of ED-1- and α-smooth muscle actin (α-SMA)-positive cells in the thickened peritoneum in the PD/MGO 3W group, suggesting that PD/MGO induced an inflammatory response. Furthermore, PD/MGO treatment for 3 weeks caused functional impairments in the peritoneal membrane. However, in comparison with the PD/MGO group, intraperitoneal administration of HUMSCs into the rats significantly ameliorated the PD/MGO-induced abdominal cocoon formation, peritoneal fibrosis, inflammation, neoangiogenesis, and ultrafiltration failure. After 3 weeks of transplantation, surviving HUMSCs were found in the peritoneum in the HUMSC-grafted rats. Thus, xenografts of HUMSCs might provide a potential therapeutic strategy in the prevention of peritoneal fibrosis. Significance: This study demonstrated that direct intraperitoneal transplantation of human umbilical mesenchymal stem cells into the rat effectively prevented peritoneal dialysis/methylglyoxal-induced abdominal cocoon formation, ultrafiltration failure, and peritoneal membrane alterations such as peritoneal thickening, fibrosis, and inflammation. These findings provide a basis for a novel approach for therapeutic benefits in the treatment of encapsulating peritoneal sclerosis.
authors.affiliation: Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Fan
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan, Republic of China.
authors.forename: Ching-Chih
authors.initials: CC
authors.lastname: Hsia
authors.affiliation: Department of Medicine, Mackay Medical College, New Taipei, Taiwan, Republic of China.
authors.forename: Kuang-Wen
authors.initials: KW
authors.lastname: Tseng
authors.affiliation: School of Medicine, I-Shou University, Kaohsiung City, Taiwan, Republic of China.
authors.forename: Chih-Kai
authors.initials: CK
authors.lastname: Liao
authors.affiliation: Laboratory Medicine Department, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Tz-Win
authors.initials: TW
authors.lastname: Fu
authors.affiliation: Department of Optometry, Shu-Zen College of Medicine and Management, Kaohsiung City, Taiwan, Republic of China.
authors.forename: Tsui-Ling
authors.initials: TL
authors.lastname: Ko
authors.affiliation: Institute of Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China Department of Medicine, Mackay Medical College, New Taipei, Taiwan, Republic of China.
authors.forename: Mei-Miao
authors.initials: MM
authors.lastname: Chiu
authors.affiliation: Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China School of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of China.
authors.forename: Yang-Hsin
authors.initials: YH
authors.lastname: Shih
authors.affiliation: Institute of Physiology, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Huang
authors.affiliation: Taipei Municipal Zhong Shan Girls High School, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Department of Planning, Ministry of Health and Welfare, Executive Yuan, Taipei, Taiwan, Republic of China Department of Internal Medicine ysfu@ym.edu.tw mdyangcc@mohw.gov.tw.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine, Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, Republic of China ysfu@ym.edu.tw mdyangcc@mohw.gov.tw.
authors.forename: Yu-Show
authors.initials: YS
authors.lastname: Fu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death; D003470:Culture Media / Q000737:chemistry; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D007274:Injections, Intraperitoneal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010530:Peritoneal Dialysis; D056627:Peritoneal Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D011765:Pyruvaldehyde; D051381:Rats; D017207:Rats, Sprague-Dawley; D014183:Transplantation, Heterologous; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism; D059631:Wharton Jelly / Q000166:cytology* / Q000378:metabolism
chemical_list: D000199:Actins; D015415:Biomarkers; D003470:Culture Media; D005353:Fibronectins; D011765:Pyruvaldehyde; C498862:Acta2 protein, rat
keywords: Mesenchymal stem cells; Peritoneal dialysis; Peritoneal fibrosis induced by dialysis; Submesothelial thickening; Transplantation; Umbilical cord