Testing and engineering safer human iPS-derived cardiac myocytes for transplantation

Funding Type: 
Early Translational IV
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Our long-term goal is to use stem cells derived from skin cells (iPS cells) to repair damaged heart tissue and ultimately to cure heart failure. In order to make this process safer, we propose to make a series of heart tissue diagnostic assays (HT-Dx) to help identify the cells that will have unwanted effects, before they are ever used on people. There is a great need for heart cell treatments, since many people are dying of heart failure. However, this process is also complicated since the heart is complex and many things could cause unwanted side effects. One problem is the cells might not survive after transplantation and cause scars. Another problem is that the cells could beat in the wrong way, causing the heart to beat abnormally (known as arrhythmia). The HT-Dx assays will allow us to grow heart tissue “on a chip” so that we can simulate heart cell transplants and determine how different cell types will behave in a transplant setting. By carefully measuring how the transplanted cells work in the HT-Dx, we hope to tell which cell lines would be most successful, even before being transplanted in a person. For instance, a person with heart failure might be able to choose between twenty different stem cell lines, and the HT-Dx could help the doctors choose the stem cell line that would do the best job. If the HT-Dx is successful, we will have safer, more effective cardiac cell transplants in the future. We hope that his will be an important step in curing heart failure.

Statement of Benefit to California: 

We aim to make the process of repairing damaged heart tissue safer by developing a series of heart tissue diagnostic assays, to identify the stem cell populations most likely to have adverse effects following transplantation before they are ever used in people. This research can benefit California in several ways. The results from our studies could facilitate new technology development within the California biotechnology industry. Our assays could provide valuable diagnostic tools to be used by biotechnology companies and hospitals in California. Furthermore, our Cardiac Reference Panel of iPS cell lines could be used for comparing and optimizing assays, which could be invaluable for biotechnology companies and researchers screening cell lines and drug compounds. We are working closely with California companies to develop new materials, microscopes, assay devices, and analytical software that could be the basis for new product lines or new businesses. If therapies do come to fruition, we anticipate that California medical centers will lead the way. Finally, the most important contribution of this study would be to improve the health of Californians by improving the predictability of success of cell transplantation. Heart disease is a major cause of mortality and morbidity in California, resulting in billions of dollars in health care costs. Our goal is to improve quality of life and increase productivity for the millions who suffer from heart disease.