Generation of human-pig chimeric renal organoids using iPSC technology

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 grou...

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Bibliographic Details
Published in:Communications biology 2024-10, Vol.7 (1), p.1278-13, Article 1278
Main Authors: Fujimori, Koki, Yamanaka, Shuichiro, Shimada, Kentaro, Matsui, Kenji, Kawagoe, Shiho, Kuroda, Takao, Ikeda, Atsushi, Inoue, Makoto, Kobayashi, Eiji, Yokoo, Takashi
Format: Article
Language:English
Subjects:
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Animals
Biomedical and Life Sciences
Cell culture
Chimera
Fetuses
Humans
Induced Pluripotent Stem Cells - cytology
Kidney - cytology
Kidneys
Life Sciences
Mice
Organoids
Organoids - cytology
Pluripotency
Progenitor cells
Swine
Transplantation, Heterologous
Transplants & implants
Xenografts
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Summary: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. Creation of chimeric renal organoids using human iPSC technology with fetal pig kidneys demonstrates inter-species coexistence and codevelopment in early kidney development, paving the way for humanized xenogeneic kidney creation for clinical use.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-06986-w