Engineering of three dimensional human hepatic tissue with microvascular network and bile duct structures

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293291
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Yokohama City University
• Principal Investigator: KOIKE Naoto 横浜市立大学, 医学(系)研究科(研究院), 客員教授 (50301081)
• Co-Investigator(Kenkyū-buntansha): 武部 貴則 横浜市立大学, 医学部, 准教授 (20612625) ; 谷口 英樹 横浜市立大学, 医学(系)研究科(研究院), 教授 (70292555)
• Research Collaborator: MURATA Souichirou 横浜市立大学, 医学部, 准教授 (40436275)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 肝再生 / 微小血管 / 胆管構築

Outline of Final Research Achievements

We created three-dimensional liver buds in vitro by co-culturing hepatic endoderm cells with endothelial and mesenchymal cells prepared from human iPSC. The liver buds were implanted into mouse cranial windows or intra-abdominal organs and then the microvascular networks and bile duct structures reconstructed in the liver buds were histologically observed. In the results, HNF4a positive hepatic cord like structures and SOX9 positive bile duct structures were observed. The canaliculus like structures were also observed within hepatic cord like structures, however, bile production could not be seen. Whereas EphB4 positive microvessels were observed in these tissues, intralobular veins and arteries could not be identified. We transplanted the human liver buds into the liver of rat cirrhosis models to examine the inhibition effects of liver fibrosis. In the results, human albumin was detected in rat serum, and an improvement of liver fibrosis was confirmed.

Free Research Field

肝胆膵外科