Department of Internal Medicine - Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory of Vascular and Regenerative Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
Department of Cell and Chemical Biology, Cancer Genomics Centre Netherlands, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
Stem Cell Reports. 2018 Mar 13;10(3):751-765. doi: 10.1016/j.stemcr.2018.01.041. Epub 2018 Mar 1.
Human pluripotent stem cell (hPSC)-derived kidney organoids may facilitate disease modeling and the generation of tissue for renal replacement. Long-term application, however, will require transferability between hPSC lines and significant improvements in organ maturation. A key question is whether time or a patent vasculature is required for ongoing morphogenesis. Here, we show that hPSC-derived kidney organoids, derived in fully defined medium conditions and in the absence of any exogenous vascular endothelial growth factor, develop host-derived vascularization. In vivo imaging of organoids under the kidney capsule confirms functional glomerular perfusion as well as connection to pre-existing vascular networks in the organoids. Wide-field electron microscopy demonstrates that transplantation results in formation of a glomerular basement membrane, fenestrated endothelial cells, and podocyte foot processes. Furthermore, compared with non-transplanted organoids, polarization and segmental specialization of tubular epithelium are observed. These data demonstrate that functional vascularization is required for progressive morphogenesis of human kidney organoids.
人多能干细胞（hPSC）衍生的肾类器官可能有助于疾病建模和肾脏替代组织的生成。然而，长期应用需要在 hPSC 系之间具有可转移性，并显著改善器官成熟度。一个关键问题是持续形态发生是否需要时间或有专利的脉管系统。在这里，我们表明，在完全定义的培养基条件下并在没有任何外源性血管内皮生长因子的情况下衍生的 hPSC 衍生的肾类器官会发展为宿主衍生的血管化。在肾脏包膜下对类器官进行体内成像证实了功能性肾小球灌注以及与类器官中预先存在的血管网络的连接。宽场电子显微镜显示，移植导致肾小球基底膜、有孔的内皮细胞和足细胞足突的形成。此外，与未移植的类器官相比，观察到管状上皮的极化和节段性特化。这些数据表明，功能性血管化对于人肾类器官的进行性形态发生是必需的。
