Human Embryonic Stem Cell Derived Cardiomyocytes: A Novel Source for Cell Therapy

ESC Congress 2003

Adult heart cells have limited regenerative capacity and therefore any significant cell loss, such as occurs during a heart attack, is mostly irreversible and may lead to the development of progressive heart failure. Congestive heart failure is one of the leading causes of morbidity and mortality in the western world, placing a significant economic burden on the health care systems. Despite advances in the medical, interventional, and surgical therapeutic measures, the prognosis for these patients remains unacceptably poor. With a chronic lack of donors limiting the number of patients who can benefit from heart transplantations, development of new therapeutic paradigms for heart failure has become imperative

A potential novel therapeutic approach for this situation may be to replace the dysfunctional or scarred tissue with new myogenic cells. However, this cell replacement strategy has been hampered by the lack of cell sources for human heart cells and by the lack of direct evidence for functional integration of donor and host tissues. We describe the establishment of a novel source of cardiomyocytes for cell therapy, the human embryonic stem cell differentiating system. Our results demonstrate that these unique cells can differentiate in the dish to generate spontaneously contracting tissue with the structural and functional properties of cardiac cells. We also demonstrate that the generated cardiac tissue can integrate in vitro with preexisting cardiac cultures as to form a single functional unit.

Human embryonic stem cells are unique cell lines that can be propagated in culture in the undifferentiated state for prolong periods while retaining the capability to differentiate into a variety of tissue types. We have previously established a cardiomyocyte differentiating system from these unique cells in which spontaneously beating areas could be observed within three-dimensional differentiating clusters of cells. Detailed structural, molecular, and functional studies established that these contracting cells are indeed human heart cells. Recently, we have expanded these observations and demonstrated that these cells have electrical properties typical of cardiomyocytes with the appropriate proteins and currents. We have further demonstrated that this system is not limited to the development of isolated heart cells but rather a small-scale functional cardiac tissue is generated with all cells beating in concert. In further studies, contracting human ES cell-derived cardiomyocytes were grafted to primary rat cardiac cultures in the culture dish. Within 24 hours clearly identified synchronous contractions were observed in all co-cultures. Long term analysis revealed that the grafted cells integrated structurally and functionally with host tissue.

Our results provide a possible new source for human cardiac tissue for future cell therapy and tissue engineering strategies attempting to regenerate functional myocardium. We also demonstrated that this tissue has the typical structural and electrophysiological properties of human heart cells and that these cells can integrate and function synchronously with preexisting cardiac cultures. Nevertheless, several obstacles must be overcome before any clinical applications from these cells can be expected. These include the need to increase the yield of heart cells during the differentiation process, the need to generate pure populations of cardiac cells, the need upscale the entire procedure in order to generate the hundred millions of cells required to replace the lost cells, the need to combat immune rejection, and the need to develop in vivo transplantation strategies.

Lior Gepstein, MD, PhD
Bruce Rappaport Faculty of Medicine, Cardiovascular Research Laboratory, Technion-Israel Institute of Technology, Haifa
Israel

Important: This press release accompanies both a presentation and an ESC press conference given at the ESC Congress 2003. Written by the investigator himself/herself, this press release does not necessarily reflect the opinion of the European Society of Cardiology