辛辛那提儿童医院医疗中心Kyle W. McCracken团队的一项最新研究揭示了通过远端肾元与输尿管芽融合整合人肾类器官收集系统。这一研究成果发表在2025年5月8日出版的国际学术期刊《细胞—干细胞》上。

研究人员描述了一个发育启发的hPSC分化系统，该系统通过与输尿管芽（UB）祖细胞的诱导肾原间质组装来解决这一缺陷，导致CD网络通过与远端小管的连接在肾类器官中功能整合。肾单位融合是立体发生的，受近端-远端肾单位模式的调节，可以通过发育途径的时间操纵来调节。这项工作为研究肾素-UB合成的原理和机制提供了一个平台，并为具有收集系统的无障碍肾素工程提供了一个框架，这是功能肾组织再生的重要一步。

据了解，肾脏通过一系列平行的肾元维持体内平衡，这些肾元在发育过程中形成了一个收集管系统，建立了代谢废物排泄的基本管道。来源于多能干细胞的人肾类器官（Human pluripotent stem cells [hPSCs]）产生缺乏CD的肾单位，并以盲端小管终止，限制了它们的功能潜力。

附：英文原文

Title: Integrating collecting systems in human kidney organoids through fusion of distal nephron to ureteric bud

Author: Min Shi, Brittney Crouse, Nambirajan Sundaram, Naomi Pode Shakked, Konrad Thorner, Nathaniel M. King, Parna Dutta, Lioba Ester, Weitao Zhang, Vinothini Govindarajah, Raphael Kopan, Cristina Cebrian, Christopher N. Mayhew, Michael A. Helmrath, Joseph V. Bonventre, Kyle W. McCracken

Issue&Volume: 2025-05-08

Abstract: Kidneys maintain homeostasis through an array of parallel nephrons, which fuse during development to a system of collecting ducts (CDs), establishing the essential luminal pathway for excretion of metabolic waste. Human kidney organoids derived from pluripotent stem cells (human pluripotent stem cells [hPSCs]) generate nephrons that lack CDs and terminate as blind-ended tubules, limiting their functional potential. Here, we describe a developmentally inspired hPSC differentiation system that addresses this deficiency through assembly of induced nephrogenic mesenchyme with ureteric bud (UB) progenitors, leading to a CD network functionally integrated in kidney organoids through fusion with the distal tubule. The nephron fusion occurs stereotypically and is regulated by proximal-distal nephron patterning, which can be modulated through temporal manipulation of developmental pathways. This work provides a platform for interrogating the principles and mechanisms underlying nephron-UB fusion and a framework for engineering unobstructed nephrons with collecting systems, an important step toward de novo generation of functional kidney tissue.

DOI: 10.1016/j.stem.2025.04.008

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(25)00143-2