Dept. of Cell Growth and Differentiation
Jun K. Yamashita (Professor)
Jun K. Yamashita M.D.,Ph.D.
The heart, blood vessels, and other elements of the cardiovascular system are important organs on which our life depends, Our laboratory aims to cover as wide a scope as possible of the cardiovascular system, from basic research to practical therapeutic application. Building on research into the differentiation pathway of cardiovascular cells, we use iPS cell technology to reproduce heart disease and other pathologies, and cardiovascular cells to develop new cardiac regenerative therapies. Our ultimate mission is to achieve the widespread practical application of our research findings.
We have pursued a range of research aimed at cardiac regeneration based on our development of methods of inducing cardiomyocytes and vascular endothelial cells from human pluripotent stem cells with world-leading levels of efficiency (Fujiwara et al., PLoS One 2011; Uosaki et al., PLoS One 2011; Ikuno et al., PLoS One 2017; Fukushima et al., PLoS One 2020). Among our successes are the production of 3D heart tissue using cell sheet technology and its transplant to a myocardial infarction model (Masumoto et al., Stem Cells 2012; Masumoto et al., Sci Rep 2014), and multiple layering of heart tissue using gelatin hydrogel microspheres (Matsuo et al., Sci Rep 2015). These technologies have immediate applications in the treatment of human heart failure; related clinical research into cardiac regenerative therapy is now nearing the stage of practical application in the cardiovascular surgery department of Kyoto University. Elsewhere, based on our identification of new myocardium-fated progenitor cells that differentiate specifically into cardiomyocytes (Takeda et al., Cell Rep 2018), we are now working to apply the findings to new cardiac regenerative therapy. In disease modeling, rather than use a simple cell model, we created a mini 3D tissue that mimics heart tissue, thereby achieving the world's first reproduction under culture conditions of the fatal arrhythmia torsade de pointes (Kawatou et al., Nature Commun 2017). This now promises to serve as an advanced model for drug safety testing and reproduction of disease pathology. Our basic research into cell differentiation mechanisms and other areas has included the cardiomyocyte proliferation mechanism (Uosaki et al., Circ Cardiovasc Genet 2013), mechanisms regulating the undifferentiated state and differentiation speed of stem cells (Liu et al., Biochem Biophys Res Commun 2019; Minakawa et al., Biochem Biophys Res Commun 2020), and the discovery of a new mechanism that coordinates cell differentiation (Minakawa et al., BioRxiv 2021). We are also working to disseminate these findings widely, and have already commercialized human cardiomyocytes and endothelial cells, differentiation induction kits, and other products based on our technologies.
To additionally make the multilayered cardiac tissue available worldwide as a commercial product for use in regenerative medicine and other areas, we are proceeding with business development through a bioventure. These activities have received strong recognition, including the 14th Award for Persons of Merit in Industry Academia Government Collaboration, cabinet office (Science Council of Japan President Award), and the President's Award from the Japan Academic Society for Ventures and Entrepreneurs. In this way, we are energetically engaged across a broad front, from highly creative basic research projects to applied research for therapeutic purposes and business development for practical utilization.
Flowchart of research based on our system for cardiovascular cell
differentiation from pluripotent stem cells