Preparation of and drug discovery studies by hepatobiliary pancreatic cancer stem cell models derived from organoid and induced pluripotent stem cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Okayama University
• Principal Investigator: Iwasaki Yoshiaki 岡山大学, 保健管理センター, 教授 (00314667)
• Co-Investigator(Kenkyū-buntansha): 笠井 智成 岡山大学, 中性子医療研究センター, 准教授 (30530191)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝胆膵がん / がん幹細胞 / オルガノイド / 人工多能性幹細胞

Outline of Final Research Achievements

We induced differentiation of mouse induced pluripotent stem cells into liver and bile duct progenitors and pancreatic progenitors via embryonic endoderm, and induced tumorigenesis of cells at each stage using a method to generate cancer stem cell models. Organoids at each stage of differentiation were also generated and induced to become cancerous in the same manner. These cells and organoids were transplanted subcutaneously and into the liver of mice to form masses. The efficiency of organoid and tumor formation was higher in undifferentiated cells, but the efficiency of tumor formation was still low, requiring further investigation of conditions for induction of differentiation and tumorigenesis. On the other hand, organoids of mouse liver and bile duct progenitor cells were induced to become cancerous and transplanted into mouse liver, but the conditions at each step need to be improved for stable tumor formation.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

遺伝的に明確かつ均一ながん幹細胞モデルの作成は、がんの生物学的な解析などの基礎的な研究に重要であり、その解析成果による臨床応用も期待される。さらに、がん幹細胞動物モデルの作成は、診断及び創薬などの臨床応用に直結する可能性を秘めている。本研究ではこれらがん幹細胞およびそのオルガノイドモデルの作成からがん幹細胞動物モデルの作成を試みたものであり、その過程に影響を及ぼす種々の要因が明らかになった。これらの要因の更なる究明によるより効率的ながん幹細胞モデルの作成が今後期待される。