2022 Fiscal Year Final Research Report

Analysis of coagulation and fibrinolytic functions and vascular endothelium-platelet interaction using disease-specific iPS cells

Research Project

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Project/Area Number	20K08710
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54010:Hematology and medical oncology-related
Research Institution	Hamamatsu University School of Medicine
Principal Investigator	SANO Hideto 浜松医科大学, 医学部, 助教 (80623842)
Co-Investigator(Kenkyū-buntansha)	浦野哲盟浜松医科大学, 医学部, 特命研究教授 (50193967) 鈴木優子浜松医科大学, 医学部, 教授 (20345812) 田中宏樹浜松医科大学, 医学部, 特任研究員 (50456563)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	線溶反応 / iPS細胞 / 血管内皮細胞 / 血小板 / 細胞動態機能
Outline of Final Research Achievements	We performed vascular endothelial cell and platelet differentiation from iPS cells derived from PAI-1-deficient patients. Regarding the differentiation stage, various differentiation methods were tried. We have confirmed that the co-culture method on stromal OP9 cells was the most efficient in endothelial differentiation. PAI-1-deficient iPS cell-derived endothelial cells showed an increase in the number of short sprouts by vascular sprouting assay, but vascular outgrowth was suppressed. Platelet differentiation is under ongoing analysis. On the other hand, when PAI-1-deficient endothelial cells were established by genome editing of a human vascular endothelial cell line, the cell dynamics and tube formation were totally different compared to control cells suggested PAI-1 would be involved in angiogenesis. To further elucidate the role of PAI-1, it is necessary to establish further iPS cells derived from PAI-1-deficient patients.
Free Research Field	生理学、血栓止血学、血管生物学
Academic Significance and Societal Importance of the Research Achievements	本研究成果として、これまでに関与が示唆されていた線溶系の血管新生への影響について、さらに踏み込んだ解析を行った。近年血管新生は、血管内皮細胞の多様性により開始・伸長・安定化の3ステップにより成立することが判明してきた。本研究の結果、PAI-1欠損内皮細胞では血管新生開始を促進するが、伸長が抑制される新たなメカニズムが示唆された。以上より、線溶系の時空間的調節により血管新生の制御の可能性が広がり、創傷治癒、腫瘍、末梢血管障害等の疾患への応用へ繋がると考えられる。