Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
Clin Exp Nephrol. 2021 Jun;25(6):574-584. doi: 10.1007/s10157-021-02030-x. Epub 2021 Mar 3.
With few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.
由于肾脏疾病的治疗方法有限，再生医学作为一种新的治疗选择越来越受到关注。最近，利用人诱导多能干细胞（hiPSC）进行肾脏再生的进展值得关注。基于对肾脏发育的认识，已经建立了 hiPSC 向两种胚胎肾脏祖细胞，即肾祖细胞（NPC）和输尿管芽（UB）的定向分化，从而能够生成肾单位和收集管类器官。此外，这些 hiPSC 衍生的祖细胞可以生成人肾脏组织，其中 NPC 衍生的肾小球和肾小管以及 UB 衍生的收集管相互连接。当将诱导的肾脏组织移植到免疫缺陷小鼠中时，会进一步进行血管化。除了用于移植的肾脏重建外，已经证明 hiPSC 衍生的 NPC 细胞治疗可改善小鼠的急性肾损伤（AKI）。针对常染色体显性多囊肾病（ADPKD）等难治性肾脏疾病，也使用疾病特异性 hiPSC 进行了疾病建模和药物发现研究。为了解决与肾脏疾病相关的并发症，已经成功生成了 hiPSC 衍生的产生促红细胞生成素（EPO）的细胞，以发现药物并开发肾脏贫血的细胞治疗。这篇综述总结了肾脏发育生物学和基于 iPSC 技术的再生医学治疗肾脏疾病的现状和未来展望。
