The project “Heart Repair with Human Tissue Engineered Myocardium” is designed to find a new option for the treatment of heart failure. Because of the shortage of donor hearts, many patients in need never receive this life-saving therapy. We are generating engineered heart muscles (EHMs) that are made from cardiomyocytes (heart muscle cells) derived from human embryonic stem cells. The ultimate goal of this work is to produce a beating human heart “patch” that can be transplanted onto damaged hearts, and help restore function.
Through the joint efforts of researchers in Dr. Joseph Wu’s laboratory at Stanford and Dr. Larry Couture’s team at City of Hope, we have developed a process that allows essentially unlimited generation of cardiomyocytes using a process that is fully compatible with eventual clinical use. Our collaborator at Gottingen University, Dr. Wolfram Zimmerman, uses these cells to produce EHMs, which are then shipped to Stanford. At Stanford, the EHMs are evaluated for their structure, overall health, and ability to generate force as measured in vitro. These EHMs are also transplanted into rodents that have been given heart attacks, to see if the EHMs can survive and improve heart function.
In the first year of this project, we compared different methods of making EHMs and the results that could be measured both in vitro and in vivo. We established a model of heart disease in rats with defective immune systems (necessary for the survival of human cells/tissues in this extremely foreign setting). We found that a specific grid-like patch design was both easier to construct than other options and was able to survive in the rat model of heart disease.
In the 2nd year, we focused on this patch design and performed a larger number of transplants. Using EHMs made from genetically engineered cells that give off a fluorescent signal, we were able to track the long-term survival of the EHMs (at least 7 months) without having to sacrifice many of the animals. Our analysis of the transplanted EHMs showed that they had survived transplantation and had taken on characteristics that made them closer to normal heart tissue. In addition, EHM transplantation resulted in improved heart function, as compared to rats that either received no transplants or received a control EHM transplant that contained dead cells.
The next phase of our project will be to evaluate the function of larger EHMs in swine model of heart disease, since these animals have hearts that are similar in size and heart rate to humans. This is a crucial step before considering translating this work into human patients.