2021 Fiscal Year Final Research Report
The development of treatment and analysis for the mechanism on cholestatic liver disease by using humanized mouse model
| Project/Area Number |
19K09064
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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 55010:General surgery and pediatric surgery-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Goto Ryoichi 北海道大学, 大学病院, 助教 (10645287)
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| Co-Investigator(Kenkyū-buntansha) |
財津 雅昭 北海道大学, 医学研究院, 客員研究員 (20768981)
渡辺 正明 北海道大学, 医学研究院, 特任講師 (40789848)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 原発性胆汁性胆管炎 / 肝移植 / ヒト化マウス / 皮膚移植 |
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| Outline of Final Research Achievements |
We identified that the prevalence of primary biliary cholangitis (PBC) among the visiting patients in our transplant unit was 9.7%. Of them, 27.8% received living donor liver transplantation (LT), and 33.9% was listed in the waiting list for deceased donor LT. The waiting list mortality was 51.2%. Deceased donor LT was performed in 20.5%. The favorable post-LT outcome was achieved.
To establish humanized mouse model, human skin grafts were transplanted to NOD/SCID/IL-2Rg-/- (NSG) and BALB/c Rag2-/- IL-2Rg-/- (BRG) mice. Although the skin grafts could not be accepted without anti-Gr-1 antibodies in NSG, BRG accepted skin grafts. In addition, BRG mice could reject the accepted skin grafts by reconstitution with human peripheral blood mononuclear cells (PBMC).
To observe the role of immunity in PBC, PBMC isolated from the patient suffering from severe PBC, were reconstituted in humanized mouse. We identified the liver injuries in the mouse suggesting the immunity affects disease onset.
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| Free Research Field |
移植免疫
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| Academic Significance and Societal Importance of the Research Achievements |
原発性胆汁性胆管炎(PBC)に代表される胆汁うっ滞性疾患は未だに原因不明の病態であり、その病態解明が待たれている。本研究では直近のPBCに対する肝移植の頻度、脳死肝移植による救命、社会復帰の成績を明らかにした。本邦では世界に比べて脳死ドナー不足が顕著であり、脳死ドナー待機中死亡が高率であることが示され、この対策が喫緊の課題であることが浮き彫りとなった。加えてその病態についてヒト化マウスによる免疫関与の可能性を示した。本研究が病態解明の足がかりとなる可能性がある。
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