Search for innovative organ transplantation without the need for relatives or HLA matching

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22648
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Tohoku University
• Principal Investigator: DEZAWA Mari 東北大学, 医学系研究科, 教授 (50272323)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: Muse細胞 / 多能性幹細胞 / 免疫抑制 / 免疫寛容 / 点滴 / 他家移植 / 臓器移植

Outline of Final Research Achievements

Muse cells are immune privileged-endogenous pluripotent stem cells. Clinical trials have been conducted by intravenous drip of donor-Muse cells without HLA matching nor immunosuppressant treatment. When donor-Muse cells were intravenously injected prior to the donor-skin transplantation, donor-skin was engrafted at 4 weeks even without immunosuppressant treatment. When B6 mouse-derived Muse cells were intravenously administered to BALB/c mice and then B6-derived bone marrow cells were transplanted to BALB/c mice, B6-hematopoietic stem cells were successfully engraftment until 20 weeks without immunosuppressant. Interestingly, in mice, MDSCs involved in immunosuppression were mobilized from the bone marrow and accumulated in the thymus and spleen. The increase of Treg number in the bone marrow and the accumulation in the spleen were also confirmed. The use of this mechanism may enable transplantation of cells and organs without HLA-matching and immunosuppressant treatment.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

Muse細胞には、傷害部位で修復に当たったMuse細胞を排除しないで長期間受容できるように、骨髄でレシピエントの免疫系に作用する機構がある。という推察が実証されれば、画期的な医療の変革が可能となる。それは、健常ドナーのMuse細胞を臓器移植の前に予め患者に点滴し、その後臓器移植を行えば、免疫拒絶もなく長期間臓器がレシピエントの体内で維持できるということを意味する。
現在の移植医療では、血縁者やHLAの合致を前提とするが、ドナーMuse細胞の事前の点滴を行うことで移植医療をこれらの条件から解放することができる。移植医療ではドナー不足などの問題があるが、その解決にも大きく働く可能性が期待される