In China, there are about one million new patients who get heart infarction each year. Heart infarction cause mass cell death of cardiac myocytes most in left ventricle. Because cardiomyocytes have almost no regenerative ability, there is no treatment which can cure heart infarction. Pluripotent stem cells have the potential to differentiate into the cells of all lineages of our body, and offer an prospective cell transplantation therapy for heart infarction.

Drs. Yue Ma and Guangju Ji's laboratories from the Institute of Biophysics, Chinese Academy of Sciences discovered that it is the retinoic acid signals that control the differentiation of atrial myocytes vs. ventricular myocytes of human embryonic stem cells. With their technologies, homogenous human atrial myocytes and ventricular myocytes are produced in the laboratory first time in history.

Left ventricle, which pumps the blood to the body, carries the most important functions of the heart, and is the region in where the fatal infarction often happens. Because atrial, pace making, and ventricular myocytes have their unique electrophysiological properties, transplanting atrial myocytes and pace making cells into ventricle would cause arrhythmias, an potential lethal complication caused by the mis-matched electrophysiological properties between transplanted cells and host ventricular tissue. Even though the methods of deriving cardiomyocytes from human embryonic stem cells have been established for almost ten years, the cardiomycoytes generated with these protocols are fair mixture of atrial, pace making and ventricular myocytes. Drs. Ma and Ji's work first time demonstrated that homogenous ventricular myocytes are direct differentiated from human embryonic stem cells. This work removed one of major hurdles in developing stem cell based transplantation therapy for heart infarction.

Human embryonic stem cell derived atrial and ventricular myocytes change the landscape of drug discovery of heart diseases and toxicity screening by providing new tools for pharmaceutical industry. Because adult cardiomyocytes do not proliferate under culture conditions, there is no available human cardiac cell line for drug discovery and toxicity screening. Pharmaceutical industry are using primary animal cardiomyocytes and animals in cardiac drug discovery and toxicity testing. Due to the physiological differences between human and animal heart cells, a significant number of drugs which already passed the test with animal heart cells failed or withdrew from the market. With this new technology, now pharmaceutical industry can screen their drug candidates with human ventricular and atrial myocytes.

"This is a milestone for stem cell based heart regeneration research, and brought fundamental changes to the drug toxicity screen in pharmaceutical industry." said by Dr. Jurgen Hesheler, the director of the Institute of Neurophysiology, University of Cologne. This work was published in April issue of Cell Research.

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