期刊
NATURE
卷 499, 期 7459, 页码 481-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12271
关键词
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资金
- Strategic Promotion of Innovative Research and Development (S-innovation) of the Japan Science and Technology Agency (JST) [62890004]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [24106510, 24689052, 22390260, 21249071, 25253079]
- Takeda Science Foundation
- Japan IDDM network
- Yokohama Foundation for Advanced Medical Science
- Grants-in-Aid for Scientific Research [25253079, 24106510, 21249071, 22390260, 24659593, 24689052, 24659785, 62890004, 25461956] Funding Source: KAKEN
A critical shortage of donor organs for treating end-stage organ failure highlights the urgent need for generating organs from human induced pluripotent stem cells (iPSCs)(1). Despite many reports describing functional cell differentiation(2-4), no studies have succeeded in generating a three-dimensional vascularized organ such as liver. Here we show the generation of vascularized and functional human liver from human iPSCs by transplantation of liver buds created in vitro (iPSC-LBs). Specified hepatic cells (immature endodermal cells destined to track the hepatic cell fate) self-organized into three-dimensional iPSC-LBs by recapitulating organogenetic interactions between endothelial and mesenchymal cells(5). Immunostaining and gene-expression analyses revealed a resemblance between in vitro grown iPSC-LBs and in vivo liver buds. Human vasculatures in iPSC-LB transplants became functional by connecting to the host vessels within 48 hours. The formation of functional vasculatures stimulated the maturation of iPSC-LBs into tissue resembling the adult liver. Highly metabolic iPSC-derived tissue performed liver-specific functions such as protein production and human-specific drug metabolism without recipient liver replacement(6). Furthermore, mesenteric transplantation of iPSC-LBs rescued the drug-induced lethal liver failure model. To our knowledge, this is the first report demonstrating the generation of a functional human organ from pluripotent stem cells. Although efforts must ensue to translate these techniques to treatments for patients, this proof-of-concept demonstration of organ-bud transplantation provides a promising new approach to study regenerative medicine.
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