Engraftment of Kidney Organoids In Vivo.
Engraftment of Kidney Organoids In Vivo.
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DOI：
10.1007/s40472-023-00397-2
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发表时间：
2023
影响因子：
2.1
通讯作者：
Dekel, Benjamin
中科院分区：
文献类型：
--
作者：
Freedman, Benjamin S;Dekel, Benjamin
肾类器官是在体外生长的类似肾单位的异质细胞结构。类器官包含不同的细胞类型，包括足细胞、近端小管和远端小管，它们位于连续的节段中，沿沿着近端至远端轴形成图案。人类类器官正在探索其作为再生移植物的潜力，作为同种异体移植和血液透析的替代品。早期的工作分析了发育中的人类肾脏组织和整个人类胚胎肾脏雏形的移植物，作为类器官植入实验的基线。当移植到免疫缺陷小鼠的肾包膜下时，肾类器官异种移植物可以形成血管化的肾小球样结构，其表现出一定程度的过滤功能。然而，缺乏适当的集合管出口和存在丰富的基质样细胞限制了这种移植物的功能，并引起了安全性问题。最近，还产生了输尿管样类器官，其延伸类似于集合管的突起。将肾单位样和输尿管样类器官与肾间质细胞沿着组合，可能为功能更强的移植物提供途径。
Kidney organoids are heterocellular structures grown in vitro that resemble nephrons. Organoids contain diverse cell types, including podocytes, proximal tubules, and distal tubules in contiguous segments, patterned along a proximal-to-distal axis. Human organoids are being explored for their potential as regenerative grafts, as an alternative to allograft transplants and hemodialysis. Earlier work, analyzing grafts of developing human kidney tissue and whole human embryonic kidney rudiments, serves as a baseline for organoid implantation experiments. When transplanted into immunodeficient mice beneath the kidney capsule, kidney organoid xenografts can form vascularized, glomerulus-like structures, which exhibit a degree of filtration function. However, the absence of an appropriate collecting duct outlet and the presence of abundant stromal-like cells limits the functionality of such grafts and raises safety concerns. Recently, ureteric-like organoids have also been generated, which extend projections that resemble collecting ducts. Combining nephron-like and ureteric-like organoids, along with renal stromal cells, may provide a path towards more functional grafts.