新加坡南洋理工大学Yun Xia、Jia Nee Foo和美国Salk研究所Juan Carlos Izpisua Belmonte合作建立了一个高效且灵活的分化方法，将人多能干细胞分化为3D的肾脏类器官。这些肾脏类器官具有肾单位状的分段结构，并且有丰富的De novo血管网络。2019年9月出版的《细胞—干细胞》发表了这项成果。

研究人员建立了一个多功能的方法，用于生成含有血管的三维（3D）肾脏类器官。研究者采用动态调节WNT信号传导来控制近端与远端肾单位节段的相对比例，产生相关水平的血管内皮生长因子A（VEGFA）以定义驻留的血管网络。通过单细胞RNA测序确定了肾单位祖细胞作为肾血管的潜在来源。这些肾脏类器官在植入后经历进一步的结构和功能成熟。使用这个肾脏类器官平台，研究者建立了常染色体隐性多囊肾病（ARPKD）的体外模型，其囊性表型可通过基因校正或药物治疗有效预防。该研究为研究人类肾脏发育，模拟疾病发病机制以及进行患者特异性药物验证提供了新途径。

据了解，人类多能干细胞衍生的肾脏类器官重塑了肾脏发育过程和组织结构，但其含有内在的局限性，例如缺乏血管管系统和功能性，这极大地妨碍了它们的应用。

附：英文原文

Title: Generation of Human PSC-Derived Kidney Organoids with Patterned Nephron Segments and a De Novo Vascular Network

Author: Jian Hui Low, Pin Li, Elaine Guo Yan Chew, Bingrui Zhou, Keiichiro Suzuki, Tian Zhang, Michelle Mulan Lian, Meng Liu, Emi Aizawa, Concepcion Rodriguez Esteban, Kylie Su Mei Yong, Qingfeng Chen, Josep M. Campistol, Mingliang Fang, Chiea Chuen Khor, Jia Nee Foo, Juan Carlos Izpisua Belmonte, Yun Xia

Issue&Volume: Volume 25 Issue 3

Abstract: Human pluripotent stem cell-derived kidney organoids recapitulate developmental processes and tissue architecture, but intrinsic limitations, such as lack of vasculature and functionality, have greatly hampered their application. Here we establish a versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, producing a correlative level of vascular endothelial growth factor A (VEGFA) to define a resident vascular network. Single-cell RNA sequencing identifies a subset of nephron progenitor cells as a potential source of renal vasculature. These kidney organoids undergo further structural and functional maturation upon implantation. Using this kidney organoid platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD), the cystic phenotype of which can be effectively prevented by gene correction or drug treatment. Our studies provide new avenues for studying human kidney development, modeling disease pathogenesis, and performing patient-specific drug validation.

DOI: 10.1016/j.stem.2019.06.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30273-5