title: Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes.
abstract: Glomerulonephritis (GN) is a major cause of renal failure. This study sought to determine whether intrarenal injection of rat mesenchymal stem cells (MSC) can preserve renal function in a progressive rat model of GN. Early in GN (day 10), fluorescently labeled rat MSC localized to more than 70% of glomeruli, ameliorated acute renal failure, and reduced glomerular adhesions. Fifty days later, proteinuria had progressed in controls to 40 +/- 25 mg/d but stayed low in MSC-treated rats (13 +/- 4 mg/d; P < 0.01). Renal function on day 60 in the MSC group was better than in medium controls. Kidneys of the MSC group as compared with controls on day 60 contained 11% more glomeruli per 1-mm(2) section of cortex but also significantly more collagen types I, III, and IV and alpha-smooth muscle actin. Approximately 20% of the glomeruli of MSC-treated rats contained single or clusters of large adipocytes with pronounced surrounding fibrosis. Adipocytes exhibited fluorescence in their cytoplasm and/or intracellular lipid droplets. Lipid composition in these adipocytes in vivo mirrored that of MSC that underwent adipogenic differentiation in vitro. Thus, in this GN model, the early beneficial effect of MSC of preserving damaged glomeruli and maintaining renal function was offset by a long-term partial maldifferentiation of intraglomerular MSC into adipocytes accompanied by glomerular sclerosis. These data suggest that MSC treatment can be a valuable therapeutic approach only if adipogenic maldifferentiation is prevented.
authors: Division of Nephrology, University Hospital RWTH Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany. utakunter@gmx.de
authors: Uta
authors: U
authors: Kunter
authors: Song
authors: S
authors: Rong
authors: Peter
authors: P
authors: Boor
authors: Frank
authors: F
authors: Eitner
authors: Gerhard
authors: G
authors: Müller-Newen
authors: Zivka
authors: Z
authors: Djuric
authors: Claudia R
authors: CR
authors: van Roeyen
authors: Andrzej
authors: A
authors: Konieczny
authors: Tammo
authors: T
authors: Ostendorf
authors: Luigi
authors: L
authors: Villa
authors: Maja
authors: M
authors: Milovanceva-Popovska
authors: Dontscho
authors: D
authors: Kerjaschki
authors: Jürgen
authors: J
authors: Floege
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000517:prevention & control*; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005355:Fibrosis; D005921:Glomerulonephritis / Q000473:pathology* / Q000628:therapy*; D007269:Injections, Intra-Arterial; D007678:Kidney Glomerulus / Q000166:cytology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009395:Nephritis, Interstitial / Q000473:pathology / Q000628:therapy; D011507:Proteinuria / Q000473:pathology / Q000628:therapy; D051381:Rats; D011917:Rats, Inbred Lew; D012077:Renal Artery