title: Portocaval shunt for hepatocyte package: challenging application of small intestinal graft in animal models.
abstract: In developing therapeutic alternatives to liver transplantation, we have used the strategy of applying a small intestinal segment as a scaffold for hepatocyte transplantation and also as a portocaval shunt (PCS) system to address both liver dysfunction and portal hypertension. The aim of this study was to investigate the feasibility of such an intestinal segment in animal models. Hepatocytes isolated from luciferase-transgenic Lewis rats were transplanted into jejunal segments of wild-type Lewis rats with mucosa removal without PCS application. Luciferase-derived luminescence from transplanted hepatocytes was stably detected for 30 days. Then, we performed autologous hepatocyte transplantation into the submucosal layer of an isolated and vascularized small intestinal segment in pigs. Transplanted hepatocytes were isolated from the resected left-lateral lobe of the liver. On day 7, hepatocyte clusters and bile duct-like structures were observed histologically. To create an intestinal PCS system in pigs, an auto-graft of the segmental ileum and interposing vessel graft were anastomosed to the portal vein trunk and inferior vena cava. However, thrombi were observed in vessels of the intestinal PCSs. We measured the correlation between infusion pressure and flow volume in whole intestines ex vivo in both species and found that the high pressure corresponding to portal hypertension was still insufficient to maintain the patency of the intestinal grafts. In conclusion, we demonstrated the feasibility of the small intestine as a scaffold for hepatocyte transplantation in rat and pig models, but PCS using an intestinal graft failed to maintain patency in a pig model.
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan; Division of Development of Advanced Treatment; Center for Development of Advanced Medical Technology; Jichi Medical University; Tochigi, Japan.
authors: Junji
authors: J
authors: Iwasaki
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan.
authors: Toshiyuki
authors: T
authors: Hata
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan.
authors: Shinji
authors: S
authors: Uemoto
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan.
authors: Yasuhiro
authors: Y
authors: Fujimoto
authors: Division of Hepato-Biliary-Pancreatic and Transplant Surgery; Department of Surgery; Graduate School of Medicine; Kyoto University; Kyoto, Japan.
authors: Hiroyuki
authors: H
authors: Kanazawa
authors: Division of Development of Advanced Treatment; Center for Development of Advanced Medical Technology; Jichi Medical University; Tochigi, Japan.
authors: Takumi
authors: T
authors: Teratani
authors: Division of Medical Skill Training; Center for Development of Advanced Medical Technology; Jichi Medical University; Tochigi, Japan.
authors: Shuji
authors: S
authors: Hishikawa
authors: Division of Development of Advanced Treatment; Center for Development of Advanced Medical Technology; Jichi Medical University; Tochigi, Japan.
authors: Eiji
authors: E
authors: Kobayashi
mesh_terms: D000818:Animals; D064592:Autografts; D005240:Feasibility Studies; D005260:Female; D022781:Hepatocytes / Q000637:transplantation*; D007082:Ileum / Q000637:transplantation; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000166:cytology / Q000637:transplantation*; D007430:Intraoperative Care; D049449:Luminescence; D008297:Male; D023421:Models, Animal; D010477:Perfusion; D011167:Portacaval Shunt, Surgical / Q000379:methods*; D011182:Postoperative Care; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow; D034421:Sus scrofa
keywords: ectopic liver; hepatocyte transplantation; intestinal scaffold; liver cirrhosis; organogenesis; pig; portal hypertension; portocaval shunt; rat
references: Microsurgery. 2010 May;30(4):302-6
references: 20309853
references: Gastroenterology. 2008 May;134(6):1655-69
references: 18471545
references: Cell Transplant. 1998 Jul-Aug;7(4):413-6
references: 9710313
references: Nat Med. 2010 Jul;16(7):814-20
references: 20543851
references: Nat Med. 2004 Jul;10(7):749-53
references: 15170210
references: Liver Transpl. 2013 Mar;19(3):328-35
references: 23280879
references: Arq Gastroenterol. 2012 Apr-Jun;49(2):143-9
references: 22767002
references: Dig Dis Sci. 2012 Sep;57(9):2430-7
references: 22588242
references: Transplantation. 2003 Aug 27;76(4):732-4
references: 12973119
references: World J Gastroenterol. 2009 May 7;15(17):2074-7
references: 19418578
references: Science. 1986 Sep 12;233(4769):1190-2
references: 2426782
references: Organogenesis. 2013 Oct 1;9(4):235-8
references: 23896578
references: Methods Mol Biol. 2010;640:525-34
references: 20645072
references: World J Gastroenterol. 2004 Jul 15;10(14):2099-102
references: 15237443
references: J Intern Med. 2012 Sep;272(3):201-23
references: 22789058
references: Biochim Biophys Acta. 2008 Feb;1782(2):61-74
references: 18187050
references: Transplantation. 2003 Jun 15;75(11):1827-32
references: 12811241
references: Nature. 1969 Aug 2;223(5205):472-6
references: 4894426
references: Surg Endosc. 1996 Nov;10(11):1075-9
references: 8881055
references: AJR Am J Roentgenol. 2012 Oct;199(4):746-55
references: 22997364
references: Liver Transpl. 2012 Jan;18(1):9-21
references: 22140063
references: Transplant Proc. 1999 Feb-Mar;31(1-2):428-9
references: 10083173
references: Transplantation. 2009 Feb 27;87(4):457-66
references: 19307780
references: Transpl Int. 2005 Jun;18(6):750-4
references: 15910305
references: Microsurgery. 2010 May;30(4):296-301
references: 20309851
references: Liver Int. 2012 Nov;32(10):1493-504
references: 22928699
references: Transpl Immunol. 2004 Apr;12(3-4):273-88
references: 15157921
references: Transplantation. 2006 Apr 27;81(8):1179-84
references: 16641605
references: J Surg Res. 2012 Mar;173(1):e11-25
references: 22099595
references: Nat Commun. 2013;4:1399
references: 23360990
references: Ann Surg. 2013 Mar;257(3):542-7
references: 22691372
references: Clin Liver Dis. 2012 Feb;16(1):133-46
references: 22321469
references: Gastroenterology. 1982 Apr;82(4):616-28
references: 7060884
references: Cell Transplant. 2013;22(2):231-42
references: 22943797
references: PLoS One. 2011 Apr 29;6(4):e19195
references: 21559442