Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis
Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis
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DOI：
10.1152/ajprenal.00587.2009
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发表时间：
2010-11-01
影响因子：
4.2
通讯作者：
Ikeda, Tomoaki
中科院分区：
文献类型：
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作者：
Tsuda, Hidetoshi;Yamahara, Kenichi;Ikeda, Tomoaki
Taguchi，Yamahara K，Ishikane S，Otani K，Nakamura A，Sai K，Ichiaru N，Sada M，Taguchi A，Hosoda H，Tsuji M，Kawachi H，Horio M，Isaka Y，Kangawa K，Takahara S，Ikeda T。同种异体胎膜间充质干细胞有助于实验性肾小球肾炎的肾脏修复。Am J Physiol Renal Physiol 299：F1004-F1013,2010。2010年8月25日首次出版；DOI：10.1152/ajprenal.00587.2009。-据报道，间充质干细胞(MSC)是治疗肾脏疾病的一种有吸引力的治疗细胞来源。最近，我们报道了大量无创获取的同种异体胎儿膜源间充质干细胞移植对后肢缺血模型的治疗作用(石根S，Ohnishi S，Yamahara K，Sada M，Harada K，Mishima K，Iwa aki K，Fujiwara M，Kitamura S，Nagaya N，Ikeda T.Stem Cells 26：2625-2633,2008)。在这里，我们研究了同种异体FM-MSC给药是否可以改善实验性肾小球肾炎的肾损伤。抗Thy1肾炎的Lewis大鼠静脉注射主要组织相容性复合体不匹配的ACI大鼠的FM-MSC(FM-MSC组)或PBS组(PBS组)。肾病大鼠在PBS组尿蛋白排泄量增加，而FM-MSC组大鼠的尿蛋白排泄量显著低于PBS组(P<；0.05比PBS组)。Fm-MSC移植显著降低活化的系膜细胞(MC)增殖、肾小球单核/巨噬细胞浸润、系膜基质聚集，以及炎症或细胞外基质相关基因的表达，包括肿瘤坏死因子-α、单核细胞趋化蛋白-1、I型胶原、转化生长因子-β、纤溶酶原激活物抑制物-1(P<；0.05与PBS组相比)。在体外，FM-MSC来源的条件培养液通过前列腺素E_2依赖机制显著降低大鼠MC中肿瘤坏死因子-α和单核细胞趋化蛋白-1的表达。这些数据表明，移植的FM-MSC通过产生旁分泌因子促进了受损肾组织的愈合过程。我们的结果表明，同种异体FM-MSC移植是治疗急性肾炎的一种有效的治疗策略。
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. Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis. Am J Physiol Renal Physiol 299: F1004-F1013, 2010. First published August 25, 2010; doi:10.1152/ajprenal.00587.2009.-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-alpha, monocyte chemoattractant protein 1 (MCP-1), type I collagen, TGF-beta, 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-alpha and MCP-1 in rat MC through a prostaglandin E2-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.