McGowan Institute for Regenerative Medicine and Pathology Department, University of Pittsburgh, Pittsburgh, Pennsylvania.
Ri.MED Foundation, Palermo, Italy.
J Tissue Eng Regen Med. 2019 Sep;13(9):1724-1731. doi: 10.1002/term.2924. Epub 2019 Jul 30.
Stem cell-derived organoids are emerging as sophisticated models for studying development and disease and as potential sources for developing organ substitutes. Unfortunately, although organoids containing renal structures have been generated from mouse and human pluripotent stem cells, there are still critical unanswered questions that are difficult to attain via in vitro systems, including whether these nonvascularized organoids have a stable and physiologically relevant phenotype or whether a suitable transplantation site for long-term in vivo studies can be identified. Even orthotopic engraftment of organoid cultures in the adult does not provide an environment conducive to vascularization and functional differentiation. Previously, we showed that the lymph node offers an alternative transplantation site where mouse metanephroi can differentiate into mature renal structures with excretory, homeostatic, and endocrine functions. Here, we show that the lymph node lends itself well as a niche to also grow human primary kidney rudiments and can additionally be viewed as a platform to interrogate emerging renal organoid cultures. Our study has a wide-ranging impact for tissue engineering approaches to rebuild functional tissues in vivo including-but not limited to-the kidney.
干细胞衍生类器官正在成为研究发育和疾病的复杂模型，并且可能成为开发器官替代物的潜在来源。不幸的是，尽管已经从鼠和人多能干细胞中生成了含有肾结构的类器官，但仍存在一些难以通过体外系统解决的关键问题，包括这些非血管化类器官是否具有稳定且具有生理相关性的表型，或者是否可以确定适合长期体内研究的合适移植部位。即使将类器官培养物原位移植到成年动物中，也不能提供有利于血管生成和功能分化的环境。此前，我们已经证明，淋巴结提供了一种替代的移植部位，在该部位，鼠后肾原基可以分化为具有排泄、稳态和内分泌功能的成熟肾结构。在这里，我们发现淋巴结也非常适合作为生长人类原肾胚基的小生境，并且还可以被视为研究新兴肾类器官培养物的平台。我们的研究对于组织工程方法具有广泛的影响，可以在体内重建功能性组织，包括但不限于肾脏。
