Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes

被引:215
作者
Kunter, Uta
Rong, Song
Boor, Peter
Eitner, Frank
Mueller-Newen, Gerhard
Djuric, Zivka
van Roeyen, Claudia R.
Konieczny, Andrzej
Ostendorf, Tammo
Villa, Luigi
Milovanceva-Popovska, Maja
Kerjaschki, Dontscho
Floege, Juergen
机构
[1] Univ Hosp RWTH Aachen, Div Nephrol, D-52057 Aachen, Germany
[2] Slovak Med Univ, Dept Clin & Expt Pharmacotherapy, Bratislava, Slovakia
[3] Univ Hosp Rheinisch Westfal Techn Hsch Aachen, Inst Biochem, Aachen, Germany
[4] Univ Vienna, Dept Pathol, A-1010 Vienna, Austria
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2007年 / 18卷 / 06期
关键词
D O I
10.1681/ASN.2007010044
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1754 / 1764
页数:11
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