Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation.
Conditioned mesenchymal stem cells attenuate progression of chronic kidney disease through inhibition of epithelial-to-mesenchymal transition and immune modulation.
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条件间充质干细胞通过抑制上皮到间质转变和免疫调节来减轻慢性肾脏疾病的进展。
DOI：
10.1111/j.1582-4934.2012.01610.x
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发表时间：
2012-12
影响因子：
5.3
通讯作者：
Lee OK
中科院分区：
文献类型：
--
作者：
Chang JW;Tsai HL;Chen CW;Yang HW;Yang AH;Yang LY;Wang PS;Ng YY;Lin TL;Lee OK
间充质干细胞（MSCs）已被证明可以改善急性肾损伤模型的结果；但MSCs是否可以延缓慢性肾脏疾病（CKD）的肾功能衰竭仍不清楚。在本研究中，我们在含有不同浓度碱性成纤维细胞生长因子、表皮生长因子和抗坏血酸2-磷酸的培养基中培养这些细胞，研究刺激这些生长因子是否会增加肝细胞生长因子（HGF）的分泌。然后，将TGF-β1处理的肾间质成纤维细胞（NRK-49F）、肾近端小管细胞（NRK-52E）和足细胞与无抗坏血酸2-磷酸或无抗坏血酸2-磷酸的条件MSCs共培养，量化条件MSCs对肾细胞的保护作用。雄性Sprague-Dawley大鼠在5/6肾切除术后立即注射1 × 106个条件化MSCs，每隔一周通过尾静脉注射一次，持续14周。发现碱性成纤维细胞生长因子、表皮生长因子和抗坏血酸2-磷酸促进MSCs中HGF的分泌。此外，我们发现条件MSCs对TGF-β1诱导的NRK-52E的上皮-间质转化和NRK-49F细胞的活化具有保护作用。此外，条件MSCs保护足细胞免受TGF-β1诱导的突触蛋白缺失、纤维连接蛋白诱导、细胞死亡和凋亡。移植条件化人间充质干细胞后，大鼠肌酐清除率明显升高，肾小球硬化、间质纤维化明显减少，脾细胞CD4+CD25+Foxp3+调节性T细胞计数明显升高。总之，我们的研究表明，条件性间充质干细胞通过其抗纤维化和抗炎作用来维持肾功能。移植条件间充质干细胞可能有助于治疗慢性肾病。
Mesenchymal stem cells (MSCs) have been shown to improve the outcome of acute renal injury models; but whether MSCs can delay renal failure in chronic kidney disease (CKD) remains unclear. In the present study, the were cultured in media containing various concentrations of basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2-phosphate to investigate whether hepatocyte growth factor (HGF) secretion could be increased by the stimulation of these growth factors. Then, TGF-β1-treated renal interstitial fibroblast (NRK-49F), renal proximal tubular cells (NRK-52E) and podocytes were co-cultured with conditioned MSCs in the absence or presence of ascorbic acid 2-phosphate to quantify the protective effects of conditioned MSCs on renal cells. Moreover, male Sprague-Dawley rats were treated with 1 × 106 conditioned MSCs immediately after 5/6 nephrectomy and every other week through the tail vein for 14 weeks. It was found that basic fibroblast growth factor, epidermal growth factor and ascorbic acid 2-phosphate promoted HGF secretion in MSCs. Besides, conditioned MSCs were found to be protective against TGF-β1 induced epithelial-to-mesenchymal transition of NRK-52E and activation of NRK-49F cells. Furthermore, conditioned MSCs protected podocytes from TGF-β1-induced loss of synaptopodin, fibronectin induction, cell death and apoptosis. Rats transplanted with conditioned human MSCs had a significantly increase in creatinine clearance rate, decrease in glomerulosclerosis, interstitial fibrosis and increase in CD4+CD25+Foxp3+ regulatory T cells counts in splenocytes. Together, our studies indicated that conditioned MSCs preserve renal function by their anti-fibrotic and anti-inflammatory effects. Transplantation of conditioned MSCs may be useful in treating CKD.
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影响因子：
4.5
作者：
Horwitz, E. M.;Dominici, M.
通讯作者：
Dominici, M.
DOI：
10.1111/j.1440-1746.2007.05111.x
发表时间：
2008-08-01
影响因子：
4.1
作者：
Kiyama, Shigeru;Yamada, Takuya;Takemura, Hirofumi
通讯作者：
Takemura, Hirofumi
DOI：
10.1111/j.1365-2184.1970.tb00347.x
发表时间：
1970-01-01
期刊：
CELL AND TISSUE KINETICS
影响因子：
--
作者：
FRIEDENSTEIN, AJ;CHAILAKHJAN, RK;LALYKINA, KS
通讯作者：
LALYKINA, KS
影响因子：
5.6
作者：
Kilroy, Gail E.;Foster, Sandra J.;Gimble, Jeffrey M.
通讯作者：
Gimble, Jeffrey M.
影响因子：
13.6
作者：
Kunter, Uta;Rong, Song;Floege, Juergen
通讯作者：
Floege, Juergen