Mesenchymal stem cells and endothelial progenitor cells decrease renal injury in experimental swine renal artery stenosis through different mechanisms.
Mesenchymal stem cells and endothelial progenitor cells decrease renal injury in experimental swine renal artery stenosis through different mechanisms.
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DOI：
10.1002/stem.1263
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发表时间：
2013-01
期刊：
影响因子：
5.2
通讯作者：
Lerman, Lilach O.
中科院分区：
文献类型：
--
作者：
Zhu, Xiang-Yang;Urbieta-Caceres, Victor;Krier, James D.;Textor, Stephen C.;Lerman, Amir;Lerman, Lilach O.
内皮祖细胞（EPC）和间充质干细胞（MSC）增强组织修复，但具有略微不同的特性。细胞表型如何影响这种方法在肾血管疾病中的疗效还不完全清楚。本研究验证了EPC和MSC通过钝化不同的疾病途径来保护狭窄后肾脏的假设。扩增外周血EPC和脂肪来源的MSC，并通过细胞表面标志物（例如CD 34/KDR或CD 44/CD 90）表征。在4周前肾内输注溶媒（n=7）、EPC（RAS+EPC）或MSC（RAS+MSC）（均为10×10^6，n=6）和正常对照（n=7）治疗肾动脉狭窄（RAS）10周后，对猪的单肾血流动力学和功能进行评估。离体评价肾脏疾病机制。EPC和MSC减弱内质网（ER）应激的能力也进行了研究，在孤立的ER和EPC和MSC共同培养的肾小管细胞。RAS组肾小球滤过率低于对照组，RAS+EPC组升高，RAS+MSC组进一步改善，尽管两者改善肾血流量相似。EPC显着增强肾脏生长因子表达并降低氧化应激，而MSC更显着地减轻肾脏炎症、ER应激和细胞凋亡。此外，MSC通过涉及细胞接触的机制诱导培养的肾小管细胞中caspase-3和CHOP表达的更大降低EPC和MSC通过不同的机制实现RAS中相当的肾损伤减少，尽管MSC引起肾功能的略微上级改善。这些结果支持开发基于细胞的方法来管理肾血管疾病，并建议基于肾损伤的潜在病理生理学进行细胞选择。
Endothelial progenitor cells (EPC) and mesenchymal stem cells (MSC) augment tissue repair, but possess slightly different properties. How the cellular phenotype affects the efficacy of this approach in renovascular disease is incompletely understood. This study tested the hypothesis that EPC and MSC protect the post-stenotic kidney by blunting different disease pathways. Peripheral blood EPC and adipose-derived MSCs were expanded and characterized by cell surface markers (e.g. CD34/KDR, or CD44/CD90). Single-kidney hemodynamics and function were assessed in pigs after 10 weeks of renal artery stenosis (RAS) treated 4 weeks earlier with an intra-renal infusion of vehicle (n=7), EPC (RAS+EPC) or MSC (RAS+MSC) (both 10×10^6, n=6), and normal controls (n=7). Kidney disease mechanisms were evaluated ex-vivo. The ability of EPC and MSC to attenuate endoplasmic reticulum (ER) stress was also studied in isolated ER and in tubular cells co-cultured with EPC and MSC. Glomerular filtration rate in RAS was lower than controls, increased in RAS+EPC, and further improved in RAS+MSC, although both improved renal blood flow similarly. EPC prominently enhanced renal growth-factor expression and decreased oxidative-stress, while MSC more significantly attenuated renal inflammation, ER-stress, and apoptosis. Furthermore, MSC induced a greater decrease in caspase-3 and CHOP expression in cultured tubular cells through mechanisms involving cell contact EPC and MSC achieve a comparable decrease of kidney injury in RAS by different mechanisms, although MSC elicited slightly superior improvement of renal function. These results support development of cell-based approaches for management of renovascular disease, and suggest cell selection based on the underlying pathophysiology of kidney injury.
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影响因子：
13.5
作者：
Fuest, Matthias;Willim, Karolina;Hasselblatt, Peter
通讯作者：
Hasselblatt, Peter
影响因子：
158.5
作者：
Schaechinger, Volker;Erbs, Sandra;Zeiher, Andreas M.
通讯作者：
Zeiher, Andreas M.
影响因子：
37.8
作者：
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通讯作者：
Simari, RD
影响因子：
19.7
作者：
Daghini, Elena;Primak, Andrew N.;Lerman, Lilach O.
通讯作者：
Lerman, Lilach O.
DOI：
10.1016/j.bbrc.2008.04.031
发表时间：
2008-06-13
影响因子：
3.1
作者：
Liu, Guanghui;Sun, Yingying;Ge, Zhiming
通讯作者：
Ge, Zhiming