2013年7月25日
Vascularized and functional human liver from an iPSC-derived organ bud transplant.
Nature
- 巻
- 499
- 号
- 7459
- 開始ページ
- 481
- 終了ページ
- 4
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/nature12271
- 出版者・発行元
- NATURE PUBLISHING GROUP
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). Despite many reports describing functional cell differentiation, 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. 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. 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.
- リンク情報
-
- DOI
- https://doi.org/10.1038/nature12271
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/23823721
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000322157900041&DestApp=WOS_CPL
- URL
- https://rdcu.be/cC0qR 本文へのリンクあり
- Scopus
- https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84881184980&origin=inward
- Scopus Citedby
- https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84881184980&origin=inward
- ID情報
-
- DOI : 10.1038/nature12271
- ISSN : 0028-0836
- eISSN : 1476-4687
- PubMed ID : 23823721
- SCOPUS ID : 84881184980
- Web of Science ID : WOS:000322157900041