Generation of human-pig chimeric renal organoids using iPSC technology

利用 iPSC 技术生成人猪嵌合肾类器官

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作者:Koki Fujimori, Shuichiro Yamanaka, Kentaro Shimada, Kenji Matsui, Shiho Kawagoe, Takao Kuroda, Atsushi Ikeda, Makoto Inoue, Eiji Kobayashi, Takashi Yokoo

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.

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