Elucidation of the developmental mechanism of human iPS cell-derived hematopoietic stem cells in the sheep fetal hematopoietic environment
| Project/Area Number |
18K08337
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Jichi Medical University |
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Principal Investigator |
Abe Tomoyuki 自治医科大学, 医学部, 講師 (20610364)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 多能性幹細胞 / 造血幹細胞 / 分化 / 動物体内 / 胎仔 / ヒツジ / ヒトiPS細胞 / 再生医学 / 幹細胞 / 血液内科学 / 応用動物学 / トランスレーショナルリサーチ |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(17 results)
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[Presentation] Correction of human hemophilia B gene in iPSCs by base-editing based on engineered Cas9 with broad PAM flexibility.2020
Author(s)
Hiramoto T, Kashiwakura Y, Abe T, Kamoshita N, Hayakawa M, Inaba H, Togashi T, Nishimasu H, Hanazono Y, Nureki O, Ohmori T.
Organizer
The 82nd Annual Meeting of the Japanese Society of Hematology.
Related Report
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[Presentation] Correction of human hemophilia B gene in iPSCs by base-editing approach based on engineered Cas9 with broad PAM flexibility.2020
Author(s)
Hiramoto T, Kashiwakura Y, Abe T, Kamoshita N, Hayakawa M, Inaba H, Togashi T, Nishimasu H, Hanazono Y, Nureki O, Ohmori T.
Organizer
International Society on Thrombosis and Haemostasis.
Related Report
Int'l Joint Research
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