Human Embryonic Stem Cells for Heart Regeneration — The Vital Source for Cardiovascular Repair

San Diego Regenerative Medicine Institute and Xcelthera announce the publication of ground-breaking technique on direct conversion of human embryonic stem cells into cardiac cells. Due to prevalence of heart disease worldwide and acute shortage of donor organs or human myocardial grafts, there is intense interest in developing human embryonic stem cell (hESC)-based therapy. However, realizing the developmental and therapeutic potential of human embryonic stem cells has been hindered by the inefficiency and instability of generating desired cell types from pluripotent cells through multi-lineage differentiation. The original research, titled “Efficient Derivation of Human Cardiac Precursors and Cardiomyocytes from Pluripotent Human Embryonic Stem Cells with Small Molecule Induction” funded by the National Institutes of Health, is the first to show that pluripotent human embryonic stem cells can be uniformly converted into a cardiac lineage by simple provision of small molecules. This technology breakthrough not only provides a large supply of clinical-grade human cardiac therapeutic products for myocardium regeneration and replacement therapy against heart disease and failure, but also offers means for small-molecule-mediated direct control and modulation of the pluripotent fate of human embryonic stem cells when deriving an unlimited supply of clinically-relevant lineages for regenerative medicine. The protocol of this novel technology developed from human embryonic stem cell research was published in JoVE (http://www.jove.com ), the World’s first peer-reviewed scientific video Journal through open access link.

To date, lacking of a suitable human cardiac cell source has been the major setback in regenerating the damaged human myocardium, either by endogenous cells or by cell-based transplantation or cardiac tissue engineering. The heart is the first organ developed in early embryogenesis. In the adult heart, the mature contracting cardiac muscle cells (cardiomyocytes) are terminally differentiated and unable to regenerate. Damaged cardiomyocytes are replaced by non-functional cells or scar tissues that eventually lead to heart failure or heart attack. Endogenous stem cells or stem cells derived from other sources, such as mesenchymal stem cells, umbilical cord stem cells, and cord blood cells, cannot give rise to the beating heart muscle cells. Although cell populations expressing stem cell markers have been identified in the adult heart, the minuscule quantities and growing evidences indicating that they are not genuine heart cells have caused skepticism if they can potentially be harnessed for cardiac repair. Recently, reprogrammed or trans-differentiated adult cells, which can be traced back to 80th, have been rekindled as alternatives. However, adult cell-reprogrammed or transdifferentiated cells have not only the same problems of adult cells, like accelerated aging, immune rejection, not graftable, but extremely low efficiencies (< 0.5%) and abnormality as well to be useful.

Pluripotent human embryonic stem cells proffer unique revenue to generate a large supply of cardiac cells as adequate human myocardial grafts for cell-based therapy. Human embryonic stem cells and their derivatives are considerably less immunogenic than adult cells & tissues. It is also possible to bank large numbers of human leukocyte antigen isotyped cell lines so as to improve the likelihood of a close match. However, conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, which is inefficient and uncontrollable. Only a very small fraction of pluripotent cells (< 2%) spontaneously generate cardiomyocytes. Our novel approach using small molecule direct induction of pluripotent cells offers the benefits in efficiency, stability, safety, and scale-up production over existing conventional approaches. Our ground breaking technique allows producing a large supply of human cardiac cells across the spectrum of developmental stages direct from human embryonic stem cells for cardiovascular repair. The availability of human cardiac cells in high purity and large quantity with adequate potential for myocardium regeneration will accelerate the development of effective cell-based therapy for heart disease and failure that affect millions of survivors and so far have no cure.