NEW YORK (Reuters Health) - Embryonic stem cells can be programmed to provide tumor-free heart repair in an animal model, according to researchers from the Mayo Clinic in Rochester, Minnesota.

Embryonic stem cells offer the possibility of tissue regeneration, the authors explain, but their propensity for multi-lineage differentiation also carries the potential for neoplastic growth.

Dr. Andre Terzic and associates investigated whether the tumorigenic potential could be suppressed by cardiac-restricted transgenic expression of the reprogramming cytokine TNF-alpha without interfering with the cardiogenic competence of the recipient heart.

Delivery of embryonic stem cells in increasing numbers into the myocardial parenchyma of mice was associated with an increasing rate of teratoma formation, the authors report in the February Journal of Experimental Medicine.

Cardiac-restricted transgenic expression of TNF-alpha prevented the formation of teratoma after embryonic stem cell transplantation, even at doses of 10,000 embryonic stem cells per milligram of myocardial tissue, the report indicates. Expression of TNF-alpha did not interfere with proper integration of stem cells within the host myocardium.

The cardiogenic effect of TNF-alpha (tested in vitro) required the presence of endoderm, the researchers note, and p38 appeared to be the intracellular mediator of TNF-alpha cardiogenic priming.

In a chronic model of myocardial infarction, delivery of preprogrammed cardiopoietic cells 8 weeks after ligation of the left anterior descending artery decreased infarct diameter and improved myocardial wall motion and cardiac output, the investigators say.

"This is the first example where delivery of embryonic-derived cardiac progenitors achieved proper myocardial integration without risk for unguided growth," the researchers explain.

"This work thus demonstrates that use of cardiopoietic cells eliminates reliance on host heart signaling for differentiation, a limitation that has precluded pluripotent embryonic stem cells as a safe therapeutic option," the authors conclude. "Honing cellular plasticity to nullify malignant risk therefore achieves a critical step in translation of stem cells into therapy."