Circulating traveling wave enhances the maturation of cardiomyocytes in self-organized tissue

• Project/Area Number: 17K14624
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Intelligent mechanics/Mechanical systems
• Research Institution: Osaka University
• Principal Investigator: LI Junjun 大阪大学, 医学系研究科, 特任研究員(常勤) (10723786)
• Research Collaborator: Liu Li (50380093) ; Minami Itsunari (40362537)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: pluripotent stem cells / cardiomyocytes / maturation / tissue engineering / cardiomyocyte maturation / organ on chip / iPS cell / Cardiomyocyte / Maturation / Traveling wave / pluripotent stem cell

Outline of Final Research Achievements

Cardiomyocytes derived from human iPSCs are expected to be applied not only to transplantation but also to drug discovery. However, since the cardiomyocytes obtained by the existing differentiation induction method are still immature, they are not sufficiently satisfied for the application of drug evaluation. In this research project, we aim to develop an accelerated maturation method of novel pluripotent stem cell-derived cardiomyocytes without using physical stimulation from outside. The applicant discovered the closed loop and the phenomenon that action potential propagates to acceleration by the developed device. The ohenomenon was named travling wave. Furthermore, with the training by travling wave, we aim to develop an accelerated cardiomyocyte maturation method based on the spontaneous and circulating progressive waves safely, simply and stably, that is, the development of a pluripotent stem cell-derived myocardial permanent machine.

Academic Significance and Societal Importance of the Research Achievements

This technology could be a promising substitution for harmful electrical stimulation method. It can be expected that this new technology, could be of great usefulness and importance for both researchers and industrial/clinical users in the fields of drug screening and heart regeneration.

Research Products

• [Int'l Joint Research] Perking University(中国)
• [Journal Article] Clonal Isolation of Human Pluripotent Stem Cells on Nanofibrous Substrates Reveals an Advanced Sub-clone for Cardiomyocyte Differentiation (2019)
  • Author(s): Yu, L. ; Li, J. ; , Minami, I.; Qu X.; Miyagawa S.; Fujimoto, N.; Hasegawa K.; Chen, Y.; Sawa, Y.; Kotera, H.; Liu, L.,
  • Journal Title: Advanced Healthcare Materials Volume: In press
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Low Cell-Matrix Adhesion Reveals Two Subtypes of Human Pluripotent Stem Cells. (2018)
  • Author(s): Yu, L.; Li, J.; Hong, J.; Takashima, Y.; Fujimoto, N.; Nakajima, M.; Yamamoto, A.; Dong, X.; Dang, Y.; Hou, Y.; Yang, W.; Minami, I.; Okita, K.; Tanaka, M.; Luo, C.; Tang, F.; Chen, Y.; Tang, C.; Kotera, H. & Liu, L.
  • Journal Title: Stem Cell Reports Volume: 11 Issue: 1 Pages: 142-156
  • DOI: 10.1016/j.stemcr.2018.06.003
  • NAID: 120006488610
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 組織工学技術による新規心筋成熟法の開発 (2019)
  • Author(s): 劉 莉
  • Organizer: 日本再生医療学会
• [Presentation] Generating functional anisotropic and 3D tissue-like construct using induced pluripotent stem cell-derived cardiomyocytes. (2017)
  • Author(s): Li Junjun
  • Organizer: Biomedical Engineering Society Annual Meeting
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] Ring-like cardiac tissue construct (2018)
  • Inventor(s): Liu, L.; Li, J.
  • Industrial Property Rights Holder: Liu, L.; Li, J.
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018