title: Transplantable liver production plan: "Yamaton"--liver project, Japan.
abstract: Organ grafts developed in the xenogeneic pig scaffold are expected to resolve most issues of donor safety and ethical concerns about living-donor liver transplantation in Japan. We have been working on so-called "Yamaton" projects to develop transplantable organs using genetically engineered pigs. Our goal is to produce chimeric livers with human parenchyma in such pigs. The Yamaton-Liver project demonstrated the proof of concept by showing that rat-mouse chimeric livers could develop in mice and be successfully transplanted into syngeneic or allogeneic rats. Under conventional immunosuppression, the transplanted livers showed long-term function and protection against rejection. Because chimeric liver grafts have xenogeneic components, additional strategies, such as humanization of pig genes, induction of hematopoietic chimeras in donors, and replacement of pig endothelial cells with human ones, might be required in clinical use. Our projects still need to overcome various hurdles but can bring huge benefits to patients in the future.
authors.affiliation: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hata
authors.affiliation: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Center for Development of Advanced Medical Technology; Jichi Medical University; Tochigi, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D006801:Humans; D007564:Japan; D008099:Liver / Q000254:growth & development*; D016031:Liver Transplantation; D051379:Mice; D038081:Organogenesis; D051381:Rats; D034421:Sus scrofa; D054457:Tissue Scaffolds
keywords: chimeric organ; humanized organ graft; liver transplantation; organogenesis; scaffold; swine; transgenic pig
references.citation: Ann Surg. 2003 Feb;237(2):265-72
references.pmid: 12560785
references.citation: PLoS One. 2012;7(1):e29720
references.pmid: 22247784
references.citation: Biomed Mater. 2013 Feb;8(1):010201
references.pmid: 23355718
references.citation: Liver Transpl. 2013 Mar;19(3):328-35
references.pmid: 23280879
references.citation: Nat Med. 2008 Feb;14(2):213-21
references.pmid: 18193059
references.citation: J Clin Invest. 2008 Mar;118(3):935-45
references.pmid: 18274668
references.citation: J Am Soc Nephrol. 2009 Nov;20(11):2338-47
references.pmid: 19729441
references.citation: Transplantation. 2011 Jun 27;91(12):1310-7
references.pmid: 21505379
references.citation: Lancet. 2003 Aug 30;362(9385):687-90
references.pmid: 12957090
references.citation: Am J Transplant. 2012 Mar;12(3):523-30
references.pmid: 22054061
references.citation: Ann Surg. 2013 Mar;257(3):542-7
references.pmid: 22691372
references.citation: Cell. 2010 Sep 3;142(5):787-99
references.pmid: 20813264
references.citation: Xenotransplantation. 2011 Jul-Aug;18(4):215-28
references.pmid: 21848538
references.citation: Nat Med. 2010 Jul;16(7):814-20
references.pmid: 20543851
references.citation: Nat Med. 2010 Aug;16(8):927-33
references.pmid: 20628374
references.citation: Am J Pathol. 2012 Jun;180(6):2417-26
references.pmid: 22507837
references.citation: Cell Stem Cell. 2012 Jun 14;10(6):753-758
references.pmid: 22704516
references.citation: Ann Surg. 2012 Aug;256(2):363-70
references.pmid: 22691371
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 19;110(12):4557-62
references.pmid: 23431169
references.citation: J Clin Invest. 2012 Nov;122(11):3817-23
references.pmid: 23114604
references.citation: Transplant Proc. 2012 Mar;44(2):469-72
references.pmid: 22410047
references.citation: Transplant Res. 2012 Aug 16;1(1):8
references.pmid: 23369409
references.citation: Cell Transplant. 2013;22(2):231-42
references.pmid: 22943797
references.citation: Stem Cells. 2012 Jun;30(6):1228-35
references.pmid: 22488594
references.citation: Organogenesis. 2012 Apr-Jun;8(2):41-8
references.pmid: 22699748