Heart Cells from Human Embryonic Stem Cells
By Richard Mollard, PhD

Human embryonic stem cells were first described by Jamie Thomson and his colleagues at the University of Wisconsin (USA) in 1998. Since that time, a rapidly growing number of researchers have focused their efforts upon the development of protocols capable of instructing human embryonic stem cells to become a preferred cell type for use in transplantation therapeutics. The more popular efforts have surrounded attempts to produce cardiac tissue for heart attacks, pancreatic tissue for diabetes and neural tissue for Parkinson's disease and spinal cord injuries.

Mouse embryonic stem cells were first described some 17 years earlier and as a result their culture requirements are better understood and associated handling techniques are more sophisticated. Progress using mouse embryonic stem cells as therapeutic agents to treat several animal models of human disease has thus quickly reached a more advanced stage. Reports of mouse embryonic stem cell derivatives improving heart function, curing genetic blood disease, normalizing weight, longevity and temporarily, insulin levels in diabetic mice, reducing symptoms of Parkinson's disease and partially repairing damaged spinal cords have all appeared in the scientific literature. Studies demonstrating physiological function of human embryonic stem cell derivatives in vivo , however, have been lacking.

Now, in the October edition of Nature Biotechnology , Kehat and colleagues report the production of heart tissue from human embryonic stem cells and for the fist time, meaningful physiological function of human embryonic stem cell derivatives in an animal model. In this study, transplantation of the derived heart cells was described to successfully treat pigs providing a model system of a human heart abnormality known as atrioventricular block. Atrioventricular block means that the electrical impulses responsible for eliciting communication between the heart chambers are slowed or even stopped. As a result the heart cannot function efficiently and circulation of blood through the body is compromised. Depending on the degree of block, this can lead to death. In humans, pacemakers are often employed to correct the deficit.

The study by Kehat and colleagues, described specialized culture techniques that were used to first differentiate the human embryonic stem cells into cardiac-like cells and then induce electrical signaling between these calls and rat heart muscle cells, in culture.   Following this in vitro demonstration of function appropriate to cardiac cells, the human embryonic stem cell derivatives were transplanted into a pig model with atrioventricular block. The authors could show electrical signaling of the pig heart chambers and a restored heart rhythm compatible with survival of approximately half the animals tested.

Anticipating the current debate on cell fusion (see also http://www.isscr.org/public/heart.htm ), the authors acknowledge that their work was limited in part by the failure to test for cell fusion (between the transplanted cells and the cells already existing in the pig heart) and the inability to discriminate between direct electrical effects of the cells versus indirect instructive effect upon neighboring cells. Questions regarding immune rejection were also not addressed, and the authors did not perform all the tests to exclude safety issues such as the possible development of tumors resulting from transfer of remnant human embryonic stem cells. As explained in an accompanying Nature Biotechnology commentary, for these and other reasons, it is inappropriate to suggest that electronic pacemakers may be now substituted by the biological pacemaker capabilities of such cardiac cells derived from human embryonic stem cells.

What is novel about this work, however, is that it provides important evidence to support the concept that human embryonic stem cells may represent suitable candidates for relieving heart deficiencies in a fashion compatible with survival. Furthermore, this report provides an awaited proof of principal for the belief that human embryonic stem cells will one day play an important role in cell transplantation therapeutics.

Cited References

Richard Mollard, Ph.D., is an embryonic stem cell specialist at the Institute of Reproduction and Development at the Monash University in Australia.

Updated: February 2, 2005