2019 Fiscal Year Final Research Report
Therapeutic application of BOECs in von Willebrand disease
| Project/Area Number |
17K09902
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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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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 伸明 名古屋大学, 医学部附属病院, 助教 (70637686)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | von Willebrand因子 / DDAVP / Weibel-Palade body / Factor VIII / HUVEC / BOEC / ECFC |
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| Outline of Final Research Achievements |
In this study, we used Endothelial Colony forming cells (ECFC), which was obtained by culturing vascular endothelial progenitor cells (EPCs) isolated derived directly rom the peripheral blood of VWD patients. The effect of mutant VWF gene expression due to dominant-negative inheritance was intensively studied by immunofluorescence staining of ECFC and measurement of cell supernatant or lysate of the cells by ELISA. VWF release stimulated by DDAVP in ECFC was also studied, thereby the cytological VWF transport and secretion was observed. Based on our results, cytological background of the difference in the reactivity to DDAVP per each patient could be speculated.
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| Free Research Field |
血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
von Willebrand病(VWD)の疾患頻度は血友病に次ぐとされているが、正しく診断されていない症例が多数存在する可能性が高い。また本症は優性遺伝形式を取るが、どのようなdominant-negative mechanismでVWFのmutationが疾患をもたらすのか、細胞遺伝学的に明らかになっていない。本研究により従来のTransfectionによる発現検討より生理的な優性遺伝形式を取るVWDにおけるDominant-negativeな細胞学的な機構を詳細に検討を行うことができた。今回得られたDDAVPの最適な分泌刺激方法により新たなVWD治療の基盤モデルとなることが期待された。
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