Nestin+ kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury
Nestin+ kidney resident mesenchymal stem cells for the treatment of acute kidney ischemia injury
复制标题
Nestin( ) 肾驻留间充质干细胞用于治疗急性肾缺血损伤。
DOI：
10.1016/j.biomaterials.2015.01.029
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发表时间：
2015-05-01
期刊：
影响因子：
14
通讯作者：
Xiang, Andy Peng
中科院分区：
文献类型：
--
作者：
Jiang, Mei Hua;Li, Guilan;Xiang, Andy Peng
肾间充质干细胞(MSCs)是肾脏内稳态、修复或再生的重要调节细胞。然而，由于缺乏特定的标记，这些细胞的自然分布和起始种群特性仍然难以捉摸。在这里，我们鉴定了出生后肾脏来源的巢蛋白(+)细胞，它符合所有的标准，是间充质干细胞。分离的Nestin(+)细胞表达典型的MSC细胞表面标志，包括SCA-1、CD44、CD106、NG2和PDGFR-α。它们具有自我更新能力，具有较高的克隆形成能力和广泛的增殖能力，可传代30多代。在适当的分化条件下，这些细胞可以分化为脂肪细胞、骨细胞、软骨细胞和足细胞。静脉注射入急性肾损伤小鼠后，Nestin(+)细胞通过显著降低血清肌酐和BUN峰值水平，减少受损细胞的凋亡，从而促进功能改善。此外，来自巢蛋白(+)细胞的条件培养液可以部分地通过旁分泌因子VEGF对缺血性急性肾功能衰竭起到保护作用。综上所述，我们的研究结果表明，肾内巢蛋白(+)的MSCs可以在急性肾损伤中被分化、扩增、分化和修复，这可能为了解MSCs的生物学特性和开发肾脏疾病的细胞替代疗法提供新的线索。(C)2015爱思唯尔有限公司。保留所有权利。
Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin(+) cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin(+) cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-alpha. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin(+) cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin(+) cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin(+) MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease. (C) 2015 Elsevier Ltd. All rights reserved.