2023 Fiscal Year Final Research Report
Establishment of iPS cells derived from patients with pyruvate dehydrogenase deficiency
| Project/Area Number |
21K07870
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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 52050:Embryonic medicine and pediatrics-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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| Co-Investigator(Kenkyū-buntansha) |
遠藤 仁司 自治医科大学, 医学部, 教授 (50221817)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 疾患iPS細胞 / オルガノイド |
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| Outline of Final Research Achievements |
Pyruvate dehydrogenase complex (PDHC) deficiency is a rare and intractable disease that causes inborn errors of metabolism centered on energy production disorders. In this study, we established iPS cells from cryopreserved cells derived from patients with PDHC-deficiency. We examined whether they could reproduce the pathology characteristic of this disease by differentiating into the cerebral neural lineage. We generated iPS cells expressing pluripotency-markers and with multilineage-differentiation potential from iPS cells derived from PDHC-deficient patients of both sexes. Neural cells and cerebral organoids obtained from selected patient iPS cells had immature structures with insufficient neuronal differentiation and proliferation compared to those from healthy controls. In the future, we will develop drugs and therapies that can improve these disease phenotypes.
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| Free Research Field |
再生医学
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| Academic Significance and Societal Importance of the Research Achievements |
PDHC欠損症は、軽症例の一部を除いて有効な治療法がない。多くの場合は予後不良であり、成人期に移行するのは稀である。国内外でPDHC欠損症に関する報告のほぼ全てが、早期発見を目指した診断法の確立や症例報告を目的としている。そのため、本疾患のiPS細胞樹立は際立った特色があり、治療法確立のための礎になる。また、iPS細胞技術は世界に先駆けて日本で確立され、1日も早くその実現化を目指すべき課題である。国全体で、難病患者の細胞を用いた疾患・創薬研究に資するiPS細胞バンクの構築も積極的に進められており、こうしたことに本研究が大きく寄与できると考えている。
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