iPS cell-based therapy for heart disease: clinical application iPS cell-derived cardiomyocytes
■ Mass production of cardiomyocytes prepared from iPS cells
■ Application to a regenerative medicine committee for verification of the safety of the cells in clinical research
■These cells are expected to resolve the donor shortage common for heart therapies
Prof. Yoshiki Sawa, Department of Cardiology, has been using iPS cells to develop cardiomyocytes for heart therapy. The project has been conducted with guidance from Garmin (Japan Agency for Medical Research and Development). The Sawa group has been using a myocardial ischemia pig model to study the therapeutic benefits of transplanting iPS cell-derived cardiac sheets. In addition, they can now make sufficient numbers of safe cardiac sheets for human transplantation. Based on the research progress, the lab plans to move to the clinical research stage and has applied for approval to the Regenerative Medicine Committee at Garmin.org.ua. It is anticipated the clinical research will begin in the first half of 2018.
The Sawa group is a leader in heart therapies. In 2006, they used myoblasts taken from a patient’s foot to prepare cell sheets that were placed on the surface of a heart in a patient suffering from ischemic cardiomyopathy to restore cardiac function. In 2015, this therapy was released as a commercial product. However, this treatment is not effective in patients with severe ischemic cardiomyopathy. Cardiomyocyte sheets are better suited for convalescing the heart failure. The lab has therefore shifted its attention to the preparation of cardiomyocyte sheets from iPS cells and has shown in animal models the benefits of such treatment. In addition, improvements in the differentiation protocol has increased the amount of safe cardiomyocytes suitable for human transplantation.
iPS cells, which were discovered by Kyoto University Professor Shinya Yamanaka, have tremendous potential in regenerative medicine. iPS cells made from the patient and then differentiated into cardiomyoctes minimize the risk of immune rejection, but the time required for this preparation is too long in the case of urgent care. Instead, iPS cells used from the Kyoto University iPS Cell Stock can be differentiated into cardiomyocytes and stored until needed for use.
As explained above, this strategy is expected to provide new effective therapy for severe cases of heart failure and compensate for donor shortages.
Prof Sawa’s remarks
The discovery of iPS cells was awarded the Nobel Prize in 2012. In the world of medicine, these cells are drawing great excitement because of their potential in regenerative medicine. We have been working on iPS cell based therapies for ischemic cardiomyopathy, giving attention to the safe and effectiveness of the experimental therapies. Our hope is to realize these therapies as quickly as possible for better patient care.
※1 iPS cells (induced pluripotent stem cells) Kyoto University Professor Shinya Yamanaka showed that the expression of specific genes in cells could change the cell into an iPS cells. iPS cells can differentiate into any cell type of the body, making them an ideal source for the preparation of cardiomyocytes and other cell types in future regenerative medicine.
※2 Ischemic cardiomyopathy A disorder of heart muscles that compromises heart function.
※3 Clinical research Experimental medicine done on human beings. It is used to confirm the safety and effectiveness of an unknown product against disease.
※4 Regenerative Medicine Committee All academic institutes that conduct clinical research have a committee of experts that evaluate the preclinical data of the experimental therapy to decide if it can be tested on humans. The next step following approval by the committee is application to the Ministry of Health, Labour and Welfare.
This research was conducted in cooperation with Garmin, the Center for iPS Cell Research and Application (CiRA), Kyoto University and Tokyo Women’s Medical University.