Projects

PROJECT 1

“Metabolism-Based Cell Production” Project

We have been working on the realization of cardiac regenerative medicine, in which cardiomyocytes are produced from human iPSCs and transplanted into patients with heart disease. One of the key issues in this process is the problem of “tumorigenesis” caused by the presence of residual undifferentiated iPSCs after differentiation.

To overcome this issue, we established “world-first metabolic selection systems for cardiomyocytes using special culture medium” that focuses on the differences in metabolic mechanisms of different cell types and succeeded in overcoming this issue (Cell Stem Cell 2013, Cell Metabolism 2016, Circulation Research 2017). In addition, focusing on the fact that the fatty acid synthesis pathway is activated in undifferentiated iPSCs, which are the cells responsible for tumorigenesis, we developed “a method for selective removal of undifferentiated iPSCs by fatty acid synthase inhibition” (iScience 2020, STAR Protocols 2022a). In addition, we have developed “a method to promote proliferation of human iPSCs by controlling tryptophan metabolism” (iScience 2021, STAR Protocols 2022b).

In the future, we will further aim to refine methods to efficiently differentiate and mature human iPSCs into cardiomyocytes through metabolic control.

PROJECT 2

“Cardiac Regeneration” Project

We have produced a large number of highly purified cardiomyocytes from human iPSCs (Stem Cell Reports 2017), formed cardiac spheroids (J Heart Lung Transplant 2019), and transplanted them into the hearts of animal models with heart failure. As a result, the transplanted cells were efficiently engrafted, and the cardiac function was improved with limited post-transplant arrhythmia (J Am Coll Cardiol_BTS 2021, Circulation 2024). We have also shown that engrafted cardiomyocytes metabolically matured as well as sarcomere structures in the host heart (iScience 2024). Furthermore, we have established a method to evaluate the quality of transplanted cells using culture supernatants (Stem Cell Reports 2023).

Currently, in collaboration with a venture company, we are conducting a clinical trial on human iPSC-derived cardiac spheroids transplantation for patients with ischemic cardiomyopathy (LAPiS Study, NCT04945018).

PROJECT 3

“Cardiac Organoids and Tissues Production” Project

To establish foundational technologies for research on drug discovery and disease pathophysiology, we are working on the production of adult-like cardiac organoids and tissues in culture dishes (Cell Reports Methods 2023, Biomaterials 2023, Advanced Science 2023, Advanced Healthcare Materials 2024).