2020 Fiscal Year Final Research Report
Cancer stem cell purification and drug discovery support by the overall disease model using a new PDX model
| Project/Area Number |
18H02840
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 患者腫瘍組織移植モデル / 免疫不全マウス / SIRPA / マクロファージ寛容 / がん幹細胞 |
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| Outline of Final Research Achievements |
The xenotransplantation system using immunodeficient mice, which was developed as an assay system for normal human hematopoietic stem cells, is a model for reproducing human diseases, such as stem cell purification and pathological elucidation of hematopoietic tumors and solid tumors, development of stem cell target therapy, and infection experiment model.We aimed to develop a next-generation patient-derived xenograft model that overcomes the problems of the current xenotransplantation system. In the B6 background, we introduced the Kit mutation for bone marrow niche opening and human SIPRA knock-in into Rag2 deficiency and IL2Rg deficiency, and established BRGhSK, which is the completed form of the next-generation PDX model.
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| Free Research Field |
がん幹細胞
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| Academic Significance and Societal Importance of the Research Achievements |
本課題では、これまでの知見と実績をベースに全般的疾患再現モデルを構築可能な患者腫瘍組織移植モデルを開発し、腫瘍性幹細胞純化や創薬開発支援の基盤整備を行った。我々が注目する「SIRPA-CD47を介したマクロファージ寛容」は、異種移植の理論構築を新展開させた極めて独創的かつ有意義な発見であり、これをin vivo実験系に世界で初めて導入することにより、腫瘍性幹細胞の同定感度を飛躍的に上げることができる。本システムは、種々のPDXモデルに応用可能で、さらに、樹立された疾患モデルマウスは、ヒト細胞の薬剤感受性試験、再生医療や分子標的治療・遺伝子治療の前臨床試験などに応用可能である。
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