Construction of novel strategy for clinical application to treat severe heart failure by implantation of rabbit bone marrow-derived mesenchymal stem cell sheets

• Project/Area Number: 15K10217
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Yamaguchi University
• Principal Investigator: SHIRASAWA Bungo 山口大学, 大学院医学系研究科, 教授 (80444719)
• Co-Investigator(Kenkyū-buntansha): 藏澄 宏之 山口大学, 医学部, 特別医学研究員 (50645116) ; 末廣 晃太郎 山口大学, 医学部附属病院, 助教 (10569312)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 間葉系幹細胞 / 細胞シート / 低酸素プレコンディショニング / 心筋梗塞

Outline of Final Research Achievements

We investigated the in vivo therapeutic effect of rabbit bone marrow-derived mesenchymal stem cell sheets (BM-MSC) on a rabbit old myocardial infarcted area following autologous transplantation. Functions of left ventricular and myocardial infarcted area were compared among control group, transplantation group of BM-MSC following normoxic culture condition, and transplantation group of BM-MSC following hypoxic culture condition. Functions of left ventricular was evaluated left ventricular ejection fraction and left ventricular fractioning shortening, and myocardial infarcted area was evaluated Masson's trichrome-staining. Compared with control, transplantation of BM-MSC following normoxic condition significantly enhanced functions of left ventricular and reduced myocardial infarcted area. Furthermore, compared with normoxic condition, transplantation of BM-MSC following hypoxic condition significantly enhanced functions of left ventricular and reduced myocardial infarcted area.

Research Products

• [Journal Article] Hypoxic preconditioning of human cardiosphere-derived cell sheets enhances cellular functions via activation of the PI3K/Akt/mTOR/HIF-1α pathway (2017)
  • Author(s): Yuya Tanaka, Tohru Hosoyama, Akihito Mikamo, Hiroshi Kurazumi, Arata Nishimoto, Koji Ueno, Bungo Shirasawa, Kimikazu Hamano
  • Journal Title: American Journal of Translational Research Volume: 9 Pages: 664-673
  • Peer Reviewed / Open Access
• [Journal Article] Autologous preconditioned mesenchymal stem cell sheets improve left ventricular function in a rabbit old myocardial infarction model (2016)
  • Author(s): Yuya Tanaka, Bungo Shirasawa, Yuriko Takeuchi, Daichi Kawamura, Tamami Nakamura, Makoto Samura, Arata Nishimoto, Koji Ueno, Noriyasu Morikage, Tohru Hosoyama, Kimikazu Hamano
  • Journal Title: American Journal of Translational Research Volume: 8 Pages: 2222-2233
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 低酸素プレコンディショニングにより機能増強した自己骨髄細胞シートによる心不全治療 (2016)
  • Author(s): 田中裕也、細山 徹、竹内由利子、河村大智、中村玉美、上野耕司、西本 新、森景則保、美甘章仁、濱野公一
  • Organizer: 第１１６回日本外科学会定期学術集会
  • Place of Presentation: 大阪国際会議場／リーガロイヤルホテル大阪(大阪府大阪市）
  • Year and Date: 2016-04-14