Multiple Endodermal Organoid Generation from Robustly Amplified Human Posterior Gut Progenitors

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06534
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Yokohama City University
• Principal Investigator: ZHANG Ranran 横浜市立大学, 医学研究科, 博士研究員 (10760887)
• Research Collaborator: Taniguchi Hideki ; Takebe Takanori
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: 幹細胞 / 原始腸内胚葉細胞 / 分化 / 肝臓 / 移植

Outline of Final Research Achievements

Early human developmental progenitors naturally possess robust amplification potential to ensure organ growth; thereby, are considered as a promising source for therapy due to minimal risks for tumor or ectopic tissue formation. Here, we first demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from multiple induced pluripotent stem cell (iPSC) clones. We were able to amplify storable PGECs over a number of passages up to 1021 cells, showed much more stable differentiation propensity into endodermal lineage cells. Furthermore, human PGECs were capable of producing hepatic and intestinal tissues. PGEC-liver organoid transplantation showed therapeutic potential in treating lethal liver failure. Thus, the use of PGECs may be not only a promising alternative therapeutic source of pluripotency for self-organizing endodermal organoids but also a unique approach to study the developmental biology and disease model of the human gut.

Free Research Field

肝臓再生