title: Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis.
abstract: Mesenchymal stem cells (MSC) have been reported to be an attractive therapeutic cell source for the treatment of renal diseases. Recently, we reported that transplantation of allogenic fetal membrane-derived MSC (FM-MSC), which are available noninvasively in large amounts, had a therapeutic effect on a hindlimb ischemia model (Ishikane S, Ohnishi S, Yamahara K, Sada M, Harada K, Mishima K, Iwasaki K, Fujiwara M, Kitamura S, Nagaya N, Ikeda T. Stem Cells 26: 2625-2633, 2008). Here, we investigated whether allogenic FM-MSC administration could ameliorate renal injury in experimental glomerulonephritis. Lewis rats with anti-Thy1 nephritis intravenously received FM-MSC obtained from major histocompatibility complex-mismatched ACI rats (FM-MSC group) or a PBS (PBS group). Nephritic rats exhibited an increased urinary protein excretion in the PBS group, whereas the FM-MSC group rats had a significantly lower level of increase (P < 0.05 vs. PBS group). FM-MSC transplantation significantly reduced activated mesangial cell (MC) proliferation, glomerular monocyte/macrophage infiltration, mesangial matrix accumulation, as well as the glomerular expression of inflammatory or extracellular matrix-related genes including TNF-α, monocyte chemoattractant protein 1 (MCP-1), type I collagen, TGF-β, type 1 plasminogen activator inhibitor (PAI-1) (P < 0.05 vs. PBS group). In vitro, FM-MSC-derived conditioned medium significantly attenuated the expression of TNF-α and MCP-1 in rat MC through a prostaglandin E(2)-dependent mechanism. These data suggest that transplanted FM-MSC contributed to the healing process in injured kidney tissue by producing paracrine factors. Our results indicate that allogenic FM-MSC transplantation is a potent therapeutic strategy for the treatment of acute glomerulonephritis.
authors.affiliation: Dept. of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamahara
authors.forename: Shin
authors.initials: S
authors.lastname: Ishikane
authors.forename: Kentaro
authors.initials: K
authors.lastname: Otani
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Sawai
authors.forename: Naotsugu
authors.initials: N
authors.lastname: Ichimaru
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sada
authors.forename: Akihiko
authors.initials: A
authors.lastname: Taguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuji
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Masaru
authors.initials: M
authors.lastname: Horio
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Isaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D018925:Chemokines / Q000096:biosynthesis; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005321:Extraembryonic Membranes / Q000166:cytology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology; D005921:Glomerulonephritis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000473:pathology; D050527:Mesangial Cells / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D009000:Monocytes / Q000502:physiology; D019899:Paracrine Communication / Q000502:physiology; D011507:Proteinuria / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000199:Actins; D018925:Chemokines; D017077:Culture Media, Conditioned; D016207:Cytokines; D015232:Dinoprostone; D042461:Vascular Endothelial Growth Factor A; C498862:Acta2 protein, rat