Development of new therapy for congenital metabolic disorders using functional three-dimensional liver structures constructed by stem cells from human exfoliated deciduous teeth

2014 Fiscal Year Final Research Report

• Project/Area Number: 24592696
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Kyushu University
• Principal Investigator: YANAGI Yusuke 九州大学, 医学(系)研究科(研究院), 研究員 (30596664)
• Co-Investigator(Kenkyū-buntansha): TAGUCHI Tomoaki 九州大学, 医学(系)研究科(研究院), 教授 (20197247) ; NAKAYAMA Koichi 佐賀大学, 工学(系)研究科(研究院), 教授 (50420609) ; HAYASHIDA Makoto 九州大学, 大学病院, 助教 (70452761) ; KOHASHI Kenichi 九州大学, 大学病院, 講師 (10529879) ; IHARA Kenji 大分大学, 医学(系)研究科(研究院), 教授 (80294932)
• Co-Investigator(Renkei-kenkyūsha): YAMAZA Takayoshi 九州大学, 歯学(系)研究科(研究院), 講師 (80304814)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 歯髄幹細胞 / 肝細胞移植 / 肝組織工学 / 代謝性肝疾患 / 人工臓器

Outline of Final Research Achievements

We successfully differentiated stem cells from Human Exfoliated Deciduous teeth(SHED) to hepatocyte-like cells by our culture system. SHED derived hepatocyte-like cells(SHED-Hep) showed low immunogenicity and suppression of T cells in vitro. Following these result, we xenografted SHED-Hep into carbon tetrachloride (CCl4)-induced chronic liver fibrosis model mice without immunosuppressive therapy, showing the engraftment in the recipient liver, anti-fibrotic efficacy and prolonged survival. In the next step, we fabricated 3D liver construct with human primary hepatocytes, umbilical vein endothelial cells and mesenchymal stem cells using a bio-3D printer. It’s microstructure resembled real liver tissue in histology, and it showed liver specific functions. We also succeed in biofabrication of 3D liver construct with SHED-Hep. In future, we will transplant this SHED derived construct to develop new liver regenerative therapy.

Free Research Field

再生医療