Mesenchymal stem cell with anti-inflammatory effect cultured under microgravity prevents myocardial ischemia and regenerates myocardium.

• Project/Area Number: 18K08734
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Hiroshima University
• Principal Investigator: Kurosaki Tatsuya 広島大学, 病院(医), 准教授 (40448270)
• Co-Investigator(Kenkyū-buntansha): 末田 泰二郎 広島大学, 医系科学研究科(医), 名誉教授 (10162835) ; 弓削 類 広島大学, 医系科学研究科(保), 教授 (20263676) ; 中島 歩 広島大学, 医系科学研究科(医), 共同研究講座教授 (40448262) ; 高橋 信也 広島大学, 医系科学研究科(医), 教授 (70423382)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 間葉系幹細胞 / 心筋虚血 / 抗炎症作用 / 微重力培養 / 心筋梗塞 / 心機能

Outline of Final Research Achievements

We investigated the cardioplegic effect of stem cells cultured bloodlessly under microgravity on a rat myocardial infarction model. The optimum conditions for the combined use of microgravity culture and bloodless culture using STK2 were determined. It was possible to produce morphologically homogenized mesenchymal stem cells (MSCs). The number of mesenchymal stem cells was initially high, but was considered appropriate for cost-effectiveness and avoidance of possible complications of thrombosis. It was considered that cells cultured in microgravity may improve the ejection fraction of the left ventricle compared to normal culture, but no clear significant difference could be obtained from the results of this study. Changes in angiopoietin and pdgfc were observed, and the effect on angiogenesis of microgravity cultured cells was observed.

Academic Significance and Societal Importance of the Research Achievements

心筋の虚血障害は、心筋梗塞や不整脈、弁膜症から心不全を引き起こし、生活の質の低下や生命を危険性がある重篤な病態である。近年種々の幹細胞を利用した再生医療の研究が行われていが、iPSやESを用いた研究は進んでおり今後の成果が期待されるが、これらはその生物学的特性から癌化などの危険性が否定できない。自己の体から採取した細胞を微重力並びに無血性培地で培養し、心筋梗塞の程度の軽減や修復を行うことが出来ることは、同種あるいは異種移植という問題を回避できるため非常に魅力的かつ合理的である。本研究では、微重力ならびに無血性培養した細胞での心筋梗塞の改善の可能性を見出した。今後の検討の継続が必要である

Research Products

• [Journal Article] Hypoxia-preconditioned mesenchymal stem cells prevent renal fibrosis and inflammation in ischemia-reperfusion rats (2020)
  • Author(s): Naoki Ishiuchi, Ayumu Nakashima, Shigehiro Doi, Ken Yoshida, Satoshi Maeda, Ryo Kanai, Yumi Yamada, Takeshi Ike, Toshiki Doi, Yukio Kato, Takao Masaki
  • Journal Title: Stem Cell Res Ther . Volume: 11 Issue: 1 Pages: 130-144
  • DOI: 10.1186/s13287-020-01642-6
  • Peer Reviewed
• [Journal Article] Simulated microgravity-cultured mesenchymal stem cells improve recovery following spinal cord ischemia in rats. (2019)
  • Author(s): Kurose T, Takahashi S, Otsuka T, Nakagawa K, Imura T, Sueda T, Yuge L
  • Journal Title: Stem Cell Res Volume: 41 Pages: 1-8
  • DOI: 10.1016/j.scr.2019.101601
  • Peer Reviewed / Open Access
• [Presentation] Simulated microgravity culture enhances the neuroprotective effects of mesenchymal stem cells in spinal cord ischemia. (2018)
  • Author(s): Shinya Takahashi, Tomoyuki Kurose, Kei Nakagawa Keijiro Katayama, Tatsuya Kurosaki, Yumi Kawahara, Louis Yuge, Taijiro Sueda
  • Organizer: 日本胸部外科学会総会