RRC ID 12663
Author Tsuda H, Yamahara K, Ishikane S, Otani K, Nakamura A, Sawai K, Ichimaru N, Sada M, Taguchi A, Hosoda H, Tsuji M, Kawachi H, Horio M, Isaka Y, Kangawa K, Takahara S, Ikeda T.
Title Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis.
Journal Am. J. Physiol. Renal Physiol.
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.
Volume 299(5)
Pages F1004-13
Published 2010-11
DOI 10.1152/ajprenal.00587.2009
PII ajprenal.00587.2009
PMID 20739390
MeSH Actins / metabolism Animals Blotting, Western Cell Proliferation Chemokines / biosynthesis Culture Media, Conditioned Cytokines / biosynthesis Dinoprostone / metabolism Enzyme-Linked Immunosorbent Assay Extraembryonic Membranes / cytology* Glomerular Mesangium / cytology Glomerular Mesangium / physiology Glomerulonephritis / chemically induced Glomerulonephritis / pathology Glomerulonephritis / therapy* Immunohistochemistry Kidney / cytology Kidney / pathology Mesangial Cells / physiology Mesenchymal Stem Cell Transplantation* Monocytes / physiology Paracrine Communication / physiology Proteinuria / therapy Rats Rats, Inbred Lew Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Vascular Endothelial Growth Factor A / biosynthesis
IF 3.164
Times Cited 18
Rats LEW-Tg(CAG-EGFP)1Ys(strainID=647)