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利用 iPSC 技术生成人猪嵌合肾类器官。

Generation of human-pig chimeric renal organoids using iPSC technology.

机构信息

Sumitomo Pharma Co. Ltd., Osaka, Japan.

Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.

出版信息

Commun Biol. 2024 Oct 8;7(1):1278. doi: 10.1038/s42003-024-06986-w.

Abstract

Porcine organs and human induced pluripotent stem cell (iPSC)-derived organoids as alternative organs for human transplantation have garnered attention, but both face technical challenges. Interspecies chimeric organ production using human iPSCs shows promise in overcoming these challenges. Our group successfully generated chimeric renal organoids using human iPSC-derived nephron progenitor cells (NPCs) and fetal mouse kidneys. However, the current technology is limited to rodents. Therefore, this study focused on producing human-pig chimeric renal organoids, as pigs are the most promising species for xenotransplantation. Modification of existing culture systems enables continuous renal development in both species, resulting in the successful creation of human-pig chimeric renal organoids. Moreover, this method can be applied to generate humanized xenogeneic kidneys for future clinical applications. This study provides evidence that optimizing culture conditions enables the early-stage kidney development beyond species barriers, thus laying the foundation for accelerating research on humanized xenogeneic kidney fabrication for clinical purposes.

摘要

猪器官和人诱导多能干细胞(iPSC)衍生的类器官作为人类移植的替代器官引起了关注,但两者都面临技术挑战。使用人 iPSC 的种间嵌合体器官的产生显示出克服这些挑战的希望。我们的小组成功地使用人 iPSC 衍生的肾祖细胞(NPC)和胎鼠肾脏生成嵌合肾类器官。然而,当前的技术仅限于啮齿动物。因此,本研究集中于生成人-猪嵌合肾类器官,因为猪是最有前途的异种移植物种。对现有培养系统的修改使两种物种的肾脏持续发育成为可能,从而成功地生成了人-猪嵌合肾类器官。此外,该方法可用于生成用于未来临床应用的人源化异种肾脏。本研究提供的证据表明,优化培养条件可以使肾脏在早期阶段超越物种障碍发育,从而为加速用于临床目的的人源化异种肾脏制造的研究奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d95c/11458617/cf13c3a3c660/42003_2024_6986_Fig1_HTML.jpg

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