Elucidation of the developmental mechanism of human iPS cell-derived hematopoietic stem cells in the sheep fetal hematopoietic environment

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08337
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Abe Tomoyuki 自治医科大学, 医学部, 講師 (20610364)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 多能性幹細胞 / 造血幹細胞 / 分化 / 動物体内 / 胎仔 / ヒツジ

Outline of Final Research Achievements

We have succeeded in the generation of hematopoietic stem cells (HSCs) from human iPS cell-derived mesodermal cells in fetal sheep liver (Patent No. 6861405). In this study, we attempted to clarify the generation mechanism of human hematopoietic stem cells and to apply it to an in vitro culture system. As a result, we found that human iPS cell-derived mesodermal cells differentiate into HSCs, which are characterized by long-term engraftment and multilineage differentiation, via Notch signaling in the liver of sheep fetuses (Exp Hematol., 2021). To apply the mechanism of differentiation into HSCs in sheep fetuses in vitro, further improvement of the culture method is necessary.

Free Research Field

幹細胞生物学、実験動物学

Academic Significance and Societal Importance of the Research Achievements

骨髄や臍帯血を用いた造血幹細胞移植は、がん治療や細胞移植のための有効な治療手段である。造血幹細胞のドナー不足が続く近年、新たな移植細胞源としてiPS細胞の活用が期待されているものの、iPS細胞の造血幹細胞への分化誘導はいまだに難しい。本研究により、試験管内でヒトiPS細胞から造血幹細胞を分化誘導・大量生産するための基盤となるデータが明らかとなった。また将来的に本研究を応用して、動物体内での臓器の三次元構築や、未だ作製が困難な系統の細胞の分化誘導が可能になると期待される。