Frontier of Regenerative Medicine
- iPS cell research and appiclication on severe heart failure
iPS cell-derived cardiomyocytes for patient therapies (first in human)
Currently, heart transplant is the final treatment option for severe heart failure, but a chronic lack of donors makes it necessary to find a new source for alternative treatments. iPS cell-derived cardiomyocyte sheet transplantation has been gaining traction as such a new source. Osaka University has already developed a similar cell sheet therapy using skeletal myoblasts from the patient, and this method has obtained regulatory approval for patient care. However, too many patients have not benefited from the transplantation of these sheets, because of myocardial apoptosis and fibrosis due to limited angiogenesis. Therefore, the lab is exploring iPS cell-derived cardiomyocyte sheets.
In general, we are developing new myocardial regeneration therapies using iPS cells developed by Professor Shinya Yamanaka at Kyoto University. iPS cells are pluripotent, which means they can be induced to differentiate into any cell type, and iPS cell lines for clinical application have already been made. iPS cells are attractive for myocardial regeneration, because the complication of needing a large number of myocardical cells for transplantation therapy is mitigated by their ability to proliferate indefinitly. We have developed a mass culture method that can automatically cultivate this large number, and we succeeded in inducing iPS cells to differentiate into cardiomyocytes in feeder-free conditions. The cardiomyocyte sheets made from this method showed synchronous beating with the recipient myocardium in animal models. Compared with myoblast cell sheets, iPS cell-derived cardiomyocyte sheets achieve better contraction ratio of the left ventricle, lowering left ventricular wall stress, and improving contraction function. In addition, for clinically applicable iPS cell-derived cardiomyocyte sheets, we have found several surface antigens that will help purify the cardiomyoctes for clinical application. Currently we are verifying the safety and efficacy of sheets for clinical research and clinical trials. We believe our iPS cell-derived cardiomyocyte sheets could eliminate the need for donor in heart transplantation therapy.