Transplantation of induced pluripotent stem cell-derived renal stem cells improved acute kidney injury.
Transplantation of induced pluripotent stem cell-derived renal stem cells improved acute kidney injury.
复制标题
诱导多能干细胞衍生的肾干细胞移植可改善急性肾损伤。
DOI：
10.1186/s13578-015-0040-z
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发表时间：
2015
影响因子：
7.5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Li Q;Tian SF;Guo Y;Niu X;Hu B;Guo SC;Wang NS;Wang Y
急性肾损伤（AKI）是一种发病率和死亡率都很高的严重疾病。促进损伤肾脏修复的方法已被广泛研究。利用肾内间充质干细胞或肾祖细胞（RPCs）进行细胞治疗似乎是治疗AKI的有效策略。胚胎干细胞或诱导多能干细胞（iPSCs）也被用于AKI的恢复。然而，ipsc衍生的RPCs对AKI的治疗效果尚未确定。在这项研究中，我们使用一种肾源性混合因子结合肾上皮细胞生长培养基诱导iPSCs分化为RPCs。然后建立大鼠缺血再灌注损伤（IR）模型，将ipsc衍生的rpc与水凝胶联合移植到损伤大鼠体内。接下来，我们检查了肾脏功能相关标志物和肾脏组织学来评估注射细胞的治疗效果。此外，我们还研究了ipsc衍生的rpc影响IR引起的AKI的机制。我们发现，在肾源性混合因子刺激后，在肾上皮细胞生长培养基中培养iPSCs向rpc的分化效率提高。ipsc来源的rpc移植降低了肾损伤生物标志物的水平，减轻了肾组织的坏死和凋亡，但导致肾小管形成、细胞增殖和促肾因子的表达上调。我们的研究结果表明，ipsc衍生的rpc可以通过上调肾小管的形成、促进细胞增殖、减少细胞凋亡和调节损伤肾脏的微环境来保护AKI大鼠的肾功能损害和严重的肾小管损伤。本文的在线版本（doi:10.1186/s13578-015-0040-z）包含补充材料，仅供授权用户使用。
Acute kidney injury (AKI) is a severe disease with high morbidity and mortality. Methods that promote repair of the injured kidney have been extensively investigated. Cell-based therapy with mesenchymal stem cells or renal progenitor cells (RPCs) resident in the kidney has appeared to be an effective strategy for the treatment of AKI. Embryonic stem cells or induced pluripotent stem cells (iPSCs) are also utilized for AKI recovery. However, the therapeutic effect of iPSC-derived RPCs for AKI has yet to be determined. In this study, we induced iPSCs differentiation into RPCs using a nephrogenic cocktail of factors combined with the renal epithelial cell growth medium. We then established the rat ischemia–reperfusion injury (IR) model and transplanted the iPSC-derived RPCs into the injured rats in combination with the hydrogel. Next, we examined the renal function-related markers and renal histology to assess the therapeutic effect of the injected cells. Moreover, we investigated the mechanism by which iPSC-derived RPCs affect AKI caused by IR. We showed that the differentiation efficiency of iPSCs to RPCs increased when cultured with renal epithelial cell growth medium after stimulation with a nephrogenic cocktail of factors. The transplantation of iPSC-derived RPCs decreased the levels of biomarkers indicative of renal injury and attenuated the necrosis and apoptosis of renal tissues, but resulted in the up-regulation of renal tubules formation, cell proliferation, and the expression of pro-renal factors. Our results revealed that iPSC-derived RPCs can protect AKI rat from renal function impairment and severe tubular injury by up-regulating the renal tubules formation, promoting cell proliferation, reducing apoptosis, and regulating the microenvironment in the injured kidney. The online version of this article (doi:10.1186/s13578-015-0040-z) contains supplementary material, which is available to authorized users.