Generation of Urine-Derived Induced Pluripotent Stem Cell Line from Patients with Acute Kidney Injury.

IF 1.2 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Yong Jin, Manling Zhang, Meishuang Li, Hao Zhang, Feng Zhang, Hong Zhang, Zhibao Yin, Meng Zhou, Xin Wan, Rongfeng Li, Changchun Cao
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Abstract

Acute kidney injury (AKI) is mainly characterized by rapid decline of renal function. Currently, the strategy of stem cells might be a therapy to treat AKI. The objective of this study was to obtain human urine-derived cells (HUCs) from patients with AKI, followed by establishing induced pluripotent stem (iPS) cell line. We isolated urine cells from patients with AKI and found that the cells could survive long term with epithelioid morphology and maintain a normal karyotype. The cell line had expression of renal-specific markers and renal development-related genes. After induction, the urine cells cotransfecting with TET-ON vectors were converted into iPS cells. The HUC-derived iPS (HUC-iPS) was positive for alkaline phosphatase staining, and had expression of pluripotency markers, consistent with human embryonic fibroblast-derived iPS cell. Notably, HUC-iPS could be induced to undergo directional kidney precursor cells (KPCs) differentiation under defined conditions, and transplantation of KPCs resulted in reducing kidney damage from ischemia-reperfusion injury in mice. Therefore, we successfully established HUC-iPS cell from patients with AKI and provided a novel stem cell resource for cell therapy in AKI.

急性肾损伤患者尿源性诱导多能干细胞系的生成。
急性肾损伤(Acute kidney injury, AKI)以肾功能迅速下降为主要特征。目前,干细胞策略可能是治疗AKI的一种治疗方法。本研究的目的是从AKI患者身上获得人尿源性细胞(huc),然后建立诱导多能干细胞(iPS)细胞系。我们从AKI患者身上分离出尿细胞,发现这些细胞能够长期存活并保持上皮样形态和正常核型。该细胞系表达肾脏特异性标志物和肾脏发育相关基因。诱导后,共转染TET-ON载体的尿细胞转化为iPS细胞。huc衍生的iPS (HUC-iPS)碱性磷酸酶染色阳性,表达多能性标记,与人胚胎成纤维细胞衍生的iPS细胞一致。值得注意的是,HUC-iPS可以在规定的条件下诱导定向肾前体细胞(KPCs)分化,KPCs移植可减轻小鼠缺血再灌注损伤引起的肾损伤。因此,我们成功建立了AKI患者的HUC-iPS细胞,为AKI的细胞治疗提供了新的干细胞资源。
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来源期刊
Cellular reprogramming
Cellular reprogramming CELL & TISSUE ENGINEERING-BIOTECHNOLOGY & APPLIED MICROBIOLOGY
CiteScore
2.50
自引率
6.20%
发文量
37
审稿时长
3 months
期刊介绍: Cellular Reprogramming is the premier journal dedicated to providing new insights on the etiology, development, and potential treatment of various diseases through reprogramming cellular mechanisms. The Journal delivers information on cutting-edge techniques and the latest high-quality research and discoveries that are transforming biomedical research. Cellular Reprogramming coverage includes: Somatic cell nuclear transfer and reprogramming in early embryos Embryonic stem cells Nuclear transfer stem cells (stem cells derived from nuclear transfer embryos) Generation of induced pluripotent stem (iPS) cells and/or potential for cell-based therapies Epigenetics Adult stem cells and pluripotency.
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