Publication Date:
2013-07-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takebe, Takanori -- Sekine, Keisuke -- Enomura, Masahiro -- Koike, Hiroyuki -- Kimura, Masaki -- Ogaeri, Takunori -- Zhang, Ran-Ran -- Ueno, Yasuharu -- Zheng, Yun-Wen -- Koike, Naoto -- Aoyama, Shinsuke -- Adachi, Yasuhisa -- Taniguchi, Hideki -- England -- Nature. 2013 Jul 25;499(7459):481-4. doi: 10.1038/nature12271. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan. (ttakebe@yokohama-cu.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823721" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cell Differentiation
;
Cell Lineage
;
Drug-Induced Liver Injury/therapy
;
Endothelial Cells/cytology/metabolism/transplantation
;
Gene Expression Profiling
;
Humans
;
Induced Pluripotent Stem Cells/*cytology/metabolism/transplantation
;
Liver/*blood supply/embryology/metabolism/*physiology
;
Liver Failure/therapy
;
Liver Transplantation
;
Mesoderm/cytology/metabolism/transplantation
;
Mice
;
Regenerative Medicine/*methods
;
Tissue Culture Techniques
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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