2022 Fiscal Year Final Research Report
Development of a disease model for von Hippel-Lindau syndrome to identify novel therapeutics targeting for vascular endothelial stem cell
Project/Area Number |
21K20668
|
Research Category |
Grant-in-Aid for Research Activity Start-up
|
Allocation Type | Multi-year Fund |
Review Section |
0702:Biology at cellular to organismal levels, and related fields
|
Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
Ito Hidenori 国立研究開発法人理化学研究所, バイオリソース研究センター, 基礎科学特別研究員 (10907984)
|
Project Period (FY) |
2021-08-30 – 2023-03-31
|
Keywords | VHL病患者特異的iPS細胞 / 血管オルガノイド |
Outline of Final Research Achievements |
Von Hippel Lindau (VHL) disease is a genetic disorder characterized by hemangioblastoma in many different parts of the body. Previous studies tried to develop the VHL disease model with a genetically modified mouse model, however, it was difficult to imitate the human disease characteristics. We herein induced a vascular differentiation from the patient-specific iPS(induced pluripotent stem cell)into vascular endothelial cells, which are the target cells of the disease. Then, we developed a blood vessel organoid model with the vascular endothelial cells, which sprouted blood vessels in 3D culture. We found that the patient-derived organoids induced excessive angiogenesis compared to the healthy donor-derived organoids. This model demonstrates their usefulness as the disease model and is expected to contribute to the development of novel therapeutic factors.
|
Free Research Field |
腫瘍生物学
|
Academic Significance and Societal Importance of the Research Achievements |
これまでのVHL遺伝子改変動物モデルでは、十分な疾患モデルとして確立できていないことから、患者由来のiPS細胞を用いてヒトVHL病モデルを新規に作製したことは、独自性が高く、この疾患の発症機序の解明と治療法の開発に大いに貢献できると考えられる。また、VHL病自体は遺伝病であるが、遺伝素因のない孤発性の悪性腫瘍、特に腎がんにおいてもVHL遺伝子の変異が高頻度で見出されており、重要なドライバー変異であることが明らかとなっている。本疾患モデルを用いて新規治療法を提案することは、希少疾患であるVHL病のみならず、VHL遺伝子変異が関与する他の悪性腫瘍に対する新たな治療戦略に繋がる可能性が期待できる。
|