Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes
Mesenchymal stem cells prevent progressive experimental renal failure but maldifferentiate into glomerular adipocytes
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DOI：
10.1681/asn.2007010044
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发表时间：
2007-06-01
影响因子：
13.6
通讯作者：
Floege, Juergen
中科院分区：
文献类型：
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作者：
Kunter, Uta;Rong, Song;Floege, Juergen
肾小球肾炎（GN）是肾衰竭的主要原因。本研究旨在确定肾内注射大鼠间充质干细胞（MSC）是否可以保护进行性GN大鼠模型的肾功能。在GN早期（第10天），荧光标记的大鼠MSC定位于70%以上的肾小球，改善急性肾功能衰竭，并减少肾小球粘连。50天后，对照组的蛋白尿进展至40 +/- 25 mg/d，但MSC治疗组的蛋白尿保持较低水平（13 +/- 4 mg/d; P < 0.01）。MSC组第60天的肾功能优于培养基对照组。与对照组相比，在第60天，MSC组的肾脏每1 mm（2）皮质切片中含有11%以上的肾小球，但I型、III型和IV型胶原蛋白以及α-平滑肌肌动蛋白也显著增加。大约20%的MSC处理的大鼠肾小球含有单个或成簇的大脂肪细胞，周围有明显的纤维化。脂肪细胞在其细胞质和/或细胞内脂滴中显示荧光。这些脂肪细胞在体内的脂质组成反映了在体外进行成脂分化的MSC。因此，在该GN模型中，MSC保留受损肾小球和维持肾功能的早期有益作用被肾小球内MSC长期部分分化不良为脂肪细胞并伴有肾小球硬化所抵消。这些数据表明，MSC治疗可以是一个有价值的治疗方法，只有当脂肪形成的分化不良被阻止。
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.