Fabrication of artificial vessels derived human vascular cells using the culture system of hydrostatic pressure under hypoxia
| Project/Area Number |
20K21638
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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 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
Yokoyama Utako 東京医科大学, 医学部, 主任教授 (70404994)
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| Co-Investigator(Kenkyū-buntansha) |
上野 高義 大阪大学, 大学院医学系研究科, 教授 (60437316)
金谷 知潤 大阪大学, 医学部附属病院, 特任助教 (50793262)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 再生医療 / 循環器 / メカニカルストレス / 細胞・組織 / バイオテクノロジー |
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| Outline of Research at the Start |
臓器は細胞と多様な細胞外マトリクス複合体（＝マトリクソーム）の双方が適切に配置されて本来の機能を発揮する。本研究は、超高圧低酸素培養法を用いてヒト臍帯血管平滑筋細胞由来のマトリクソームのみから成る人工血管を開発することを目的として、超高圧低酸素を感受する分子機序を解明し、血管として最適なマトリクソームを構築する条件を見出す。さらに、大型動物への移植で耐圧性や適合性、成長性を検討する。
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| Outline of Final Research Achievements |
Although the development of tissue engineering has been progressing in recent years, it is difficult to fabricate blood vessels from scaffoldless biomaterials, which require high mechanical properties such as elasticity and rigidity. In this study, we demonstrated that periodic ultrahigh-pressure hydrostatic pressure culture under hypoxia enabled to fabrication of implantable artificial blood vessels composed solely of human umbilical cord vascular smooth muscle cells. It was shown that cells were self-organized by promoting cell-cell adhesion, cell-extracellular matrix adhesion, and extracellular matrix cross-linking by the ultrahigh-pressure hypoxic culture method.
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| Academic Significance and Societal Importance of the Research Achievements |
血管疾患の罹患者は多く、より生体適合性の高い人工血管が求められている。足場材料を使用しない細胞のみから構成される人工血管は、より生理的な細胞外マトリックスが構築される点から高い生体適合性が期待される。本研究で開発した超高圧低酸素培養法は細胞を自己組織化できる可能性を有することが示されたことから、今後循環器疾患のみならず他の分野での代替組織の構築にも寄与することが期待される。
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Multilayered human skeletal muscle myoblast sheets promote the healing process after colonic anastomosis in rats2021
Author(s)
Nakamura T, Yokoyama U, Kanaya T, Ueno T, Yoda T, Ishibe A, Hidaka Y. Umemura M, Takayama T, Kaneko M, Miyagawa S, Sawa Y, Endo I, Ishikawa Y.
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Journal Title
Cell Transplantation
Volume: 30
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Scaffold-free tissue-engineered arterial grafts derived from human skeletal myoblasts.2021
Author(s)
Saito J, Yokoyama U, Nakamura T, Kanaya T, Ueno T, Naito Y, Takayama T, Kaneko M, Miyagawa S, Sawa Y, and Ishikawa Y
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Journal Title
Artif Organs
Volume: -
Issue: 8
Pages: 919-932
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Excessive EP4 signaling in smooth muscle cells induces abdominal aortic aneurysm by amplifying inflammation2020
Author(s)
Hiromi T, Yokoyama U, Kurotaki D, Mamun A, Ishiwata R, Ichikawa Y, Nishihara H, Umemura M, Fujita T, Yasuda S, Minami T, Goda M, Uchida K, Suzuki S, Takeuchi I, Masuda M, Breyer M, Tamura T, and Ishikawa Y
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Journal Title
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 40
Issue: 6
Pages: 1559-1573
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fibulin-1 Integrates Subendothelial Extracellular Matrices and Contributes to Anatomical Closure of the Ductus Arteriosus.2020
Author(s)
Ito S, Yokoyama U, Nakakoji T, Cooley MA, Sasaki T, Hatano S, Kato Y, Saito J, Nicho N, Iwasaki S, Umemura M, Fujita T, Masuda M, Asou T, and Ishikawa Y
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 40
Issue: 9
Pages: 2212-2226
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 先天性心疾患における肺静脈狭窄の組織学的検討2022
Author(s)
Yuji Naito, Saki Iida, Tomoko Furuta, Sayuki Oka, Tomoyuki Kojima, Motonori Ishido, Hideto Iwahuchi, Ikai Akio, Kisaburo Sakamoto, Utako Yokoyama
Organizer
第58回日本小児循環器学会総会・学術集会
Related Report
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[Book] 動脈管開存症2021
Author(s)
南沢享、横山詩子
Total Pages
323
Publisher
メジカルビュー社
ISBN
9784758319690
Related Report
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[Book] Fabrication of implantable human arterial graft by periodic hydrostatic pressure.2020
Author(s)
Saito J, Yokoyama U, Takayama T, Ito H, Tadokoro T, Sugo Y, Kurasawa K, Ogawa M, Miyagi E, Taniguchi H, Kaneko M, Ishikawa Y.
Total Pages
398
Publisher
Springer
ISBN
9789811511851
Related Report
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[Book] Antenatal administration of betamethasone contributes to intimal thickening of the ductus arteriosus.2020
Author(s)
Kemmotsu T, Yokoyama U, Saito J, Ito S, Uozumi A, Iwasaki S, Nishimaki S, Ito S, Masuda M, Asou T, Ishikawa Y.
Total Pages
398
Publisher
Springer
ISBN
9789811511851
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