Rapid in vivo maturation of Biotube vascular grafts by giant drops patching of adipose-drived stromal cells

• Project/Area Number: 26861114
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular surgery
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yamanami Masashi 京都府立医科大学, 医学部附属病院, 専攻医 (30438204)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 小口径代用血管 / 生体内組織工学 / 脂肪由来間葉系幹細胞 / バイオチューブ / 小口径人工血管 / 組織工学 / 再生医療 / 生体内組織形成術 / 脂肪由来間質系幹細胞

Outline of Final Research Achievements

Adipose-derived stromal cells (ADSCs) is considered to be one of the most promising cell sources for use in vascular tissue regeneration because of their angiogenic potential. In this study, giant drops of ADSC aggregates were used for the application to enhancement of in vivo maturation of BIOTUBEs, in-body tissue engineered autologous vascular grafts.
ADSCs from subcutaneous fat of GFP transgenic rats could self-aggregate single spheroid. BIOTUBEs, which were prepeard by in-vivo tissue engineering, were auto-implanted to abdominal aortas with outer surface patching of the ADSC drops. After 3 weeks implantation, the GFP expressing cells, reached its luminal surface, were converted to endothelial cell marker positive cells and completely lining the surface, whereas it took 3 months to achieve endothelialization in traditional BIOTUBE without patching.
Rapid maturation with endothelialization of BIOTUBE grafts was achieved by patching of giant drops of ADSCs spheroids.

Research Products

• [Journal Article] Development of tissue-engineered self-expandable aortic stent grafts (Bio stent grafts) using in-body tissue architecture technology in beagles. (2015)
  • Author(s): Kawajiri H, Mizuno T, Moriwaki T, Ishibashi-Ueda H, Yamanami M, Kanda K, Yaku H, Nakayama Y.
  • Journal Title: J Biomed Mater Res B Appl Biomater. Volume: 103(2) Issue: 2 Pages: 381-386
  • DOI: 10.1002/jbm.b.33218
  • Peer Reviewed
• [Journal Article] Implantation study of a tissue-engineered self-expanding aortic stent graft (bio stent graft) in a beagle model. (2015)
  • Author(s): Kawajiri H, Mizuno T, Moriwaki T, Iwai R, Ishibashi-Ueda H, Yamanami M, Kanda K, Yaku H, Nakayama Y.
  • Journal Title: J Artif Organs. Volume: 18(1) Issue: 1 Pages: 48-54
  • DOI: 10.1007/s10047-014-0796-7
  • Peer Reviewed
• [Journal Article] Preparation of an autologous heart valve with a stent (stent-biovalve) using the stent eversion method (2014)
  • Author(s): Mizuno T, Takewa Y, Sumikura H, Ohnuma K, Moriwaki T, Yamanami M, Oie T, Tatsumi E, Uechi M, Nakayama Y
  • Journal Title: J Biomed Mater Res B Appl Biomater Volume: Dec 9 Issue: 5 Pages: 1-10
  • DOI: 10.1002/jbm.b.33086
  • Peer Reviewed
• [Journal Article] In-body tissue engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding (2014)
  • Author(s): Nakayama Y, Takewa Y, Sumukura H, Yamanami M, Matsui Y, Oie T, Kishimoto Y, Arakawa M, Ohnuma K, Kanda K, Tatsumi E
  • Journal Title: J Biomed Mater Res B Appl Biomater Volume: (in press) Issue: 1 Pages: 1-10
  • DOI: 10.1002/jbm.b.33186
  • Peer Reviewed / Open Access
• [Presentation] いつでも使用可能な異種由来自己再生型小口径代用血管『バイオチューブ・マトリックス』の開発 (2016)
  • Author(s): 山南将志、河崎貴宣、上大介、渡辺太治、神田圭一、五條理志、夜久均
  • Organizer: 第54回日本人工臓器学会大会
  • Place of Presentation: 鳥取県米子市
  • Year and Date: 2016-11-24
• [Presentation] The Development of Xenogenic, Self-Organizing Small-Diameter Vascular Graft Using "Biotube Matrix" (2016)
  • Author(s): Yamanami M, Kawasaki T, Kami D, Watanabe T, Kanda K, Gojo S, Yaku H
  • Organizer: XLIII Annual Congress of the European Society for Artificial Organs
  • Place of Presentation: ワルシャワ、ポーランド
  • Year and Date: 2016-09-14
  • Int'l Joint Research
• [Presentation] 『バイオチューブ・マトリックス』を活用した異種由来自己再生型小口径代用血管の開発 (2016)
  • Author(s): 山南将志、河崎貴宣、上大介、渡辺太治、神田圭一、五條理志、夜久均
  • Organizer: 第44回日本血管外科学会学術集会
  • Place of Presentation: 東京都港区
  • Year and Date: 2016-05-26
• [Presentation] 自由に設計でき、Shelf Ready Graftとして利用可能な再生型小口径代用血管の開発 (2016)
  • Author(s): 山南将志、河崎貴宣、上大介、渡辺太治、神田圭一、五條理志、夜久均
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2016-03-17
• [Presentation] Shelf Ready Graft としての使用を目指した異種バイオチューブ小口径代用血管(XenoBiotube)の開発 (2015)
  • Author(s): 山南将志、渡辺太治、森本和樹、川尻英長、坂井修、神田圭一、夜久均
  • Organizer: 第53回日本人工臓器学会大会
  • Place of Presentation: 東京都文京区
  • Year and Date: 2015-11-19
• [Presentation] Shelf Ready Graft としての使用を目指した小口径代用血管の開発：異種バイオチューブ（XenoBiotube）動物移植実験 (2015)
  • Author(s): 山南将志、渡辺太治、川尻英長、坂井修、神田圭一、夜久均
  • Organizer: 第68回日本胸部外科学会定期学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2015-10-17
• [Presentation] Development of Shelf-ready Xenogeneic Vascular Grafts; XenoBiotubes (2015)
  • Author(s): Yamanami M, Watanabe T, Kawajiri H, Kanda K, Nakayama Y, Yaku H.
  • Organizer: XLII Annual ESAO Conference (European Society for Artificial Organs)
  • Place of Presentation: Leuven, Belgium.
  • Year and Date: 2015-09-02
• [Presentation] 超小口径バイオチューブの長期移植評価. (2014)
  • Author(s): 山南将志、岩井良輔、川尻英長、圓見純一郎、飯田秀博、神田圭一、夜久均、中山泰秀.
  • Organizer: 第52回日本人工臓器学会大会.
  • Place of Presentation: 札幌市
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] 体内で作製した結合組織膜(Biosheet)は修復材料としての自己心膜の代用になり得る. (2014)
  • Author(s): 山南将志、水野壮司、渡辺太治、川尻英長、坂井修、神田圭一、夜久均、中山泰秀.
  • Organizer: 第67回日本胸部外科学会定期学術集会.
  • Place of Presentation: 福岡市
  • Year and Date: 2014-09-30 – 2014-10-03
• [Presentation] Long term auto implantation of autologous tissue small caliber vascular grafts (Biotubes). (2014)
  • Author(s): Yamanami M, Kawajiri H, Mizuno T, Iwai R, Watanabe T, Kanda K, Yaku H, Nakayama Y.
  • Organizer: XLI Annual ESAO Congress (European Society for Artificial Organs).
  • Place of Presentation: Rome, Italy.
  • Year and Date: 2014-09-17 – 2014-09-20
• [Presentation] Long-term performance of autologous tissue ultra-small-caliber vascular grafts (biotubes) in a rat abdominal aorta replacement model. (2014)
  • Author(s): Yamanami M, Kawajiri H, Mizuno T, Iwai R, Enmi J, Iida H, Watanabe T, Kanda K, Yaku H, Nakayama Y.
  • Organizer: ESC Congress 2014. (European Society of Cardiology)
  • Place of Presentation: Barcelona, Spain.
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] バイオチューブ超小口径代用血管移植後の長期開存性評価. (2014)
  • Author(s): 山南将志、水野壮司、神田圭一、夜久均、中山泰秀.
  • Organizer: 第42回日本血管外科学会学術総会.
  • Place of Presentation: 青森市
  • Year and Date: 2014-05-21 – 2014-05-23
• [Presentation] Long-term evaluation of autologous tissue small-caliber vascular grafts (biotubes) in a rat abdominal aorta replacement model. (2014)
  • Author(s): Yamanami M, Kawajiri H, Mizuno T, Iwai R, Watanabe T, Kanda K, Yaku H, Nakayama Y.
  • Organizer: 63ed International Congress of the European Society for Cardiovascular and Endovascular Surgery (ESCVS).
  • Place of Presentation: Nice, France.
  • Year and Date: 2014-04-24 – 2014-04-27