2022 Fiscal Year Final Research Report
Regenerative capacity of intrinsic stem cells subjected to disease-causing gene mutations
| Project/Area Number |
20K21526
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Kobe University |
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Principal Investigator |
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Keywords | 先天性疾患 / 組織欠損 / 内在性幹細胞 / 遺伝子変異 / ヒルシュスプルング病 |
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| Outline of Final Research Achievements |
In this study, we evaluated the tissue regeneration capacity of intrinsic stem cells in congenital diseases. As a model system, we chose to examine Hirschsprung disease (HSCR). HSCR is characterized by the congenital absence of the enteric ganglia in the distal gut and caused by dysfunction of enteric neural stem cells. We generated a HSCR mouse model in which a disease causing mutation can be removed in a conditional fashion. We found that, after removal of the mutation, enteric neural stem cells participated in neurogenesis, which led to regeneration of the enteric nervous system. These findings demonstrate that, once the disease causing mutation is eliminated, intrinsic stem cells can contribute to the regeneration of tissues and prevent tissue loss.
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| Free Research Field |
神経発生
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| Academic Significance and Societal Importance of the Research Achievements |
難治性HSCRの克服を目指し、ES細胞やiPS細胞由来から誘導された腸管神経前駆細胞を腸管に移植する細胞補充療法の開発が始まっている。しかし、難治性HSCRでは、細胞を移植すべき腸管が極めて長いことに加え、移植した細胞が生後の腸に生着しにくいという大きな問題を抱えている。本研究では、内在性の腸管神経幹細胞を治療すれば組織再生が誘導されることが明らかとなり、HSCRの新規治療法として内在性幹細胞の応用が有用な戦略になり得ることが示された。また、この結果は、他の先天性疾患でも同様のことが起こり得る可能性を示唆しており、先天性疾患の治療法に新たな可能性を提示する。
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