Scientists Stimulate In Situ Epicardial Progenitor Cells to Generate Cardiomyocytes

Researchers have managed to stimulate a dormant population of progenitor cells residing in the outer wall of adult hearts to transform into cardiomyocytes capable of helping restore the function of damaged myocardial tissue after a heart attack.  Although the gene reactivation approach developed by a University College London-led team isn’t particularly efficient, the researchers stress that it lays the groundwork for identifying additional chemical or natural triggers capable of further increasing the numbers of epicardium-derived progenitor cells (EPDCs) that transform into cardiomyocytes after heart damage.

The team reports on its achievement to date in Nature in a paper titled “De novo cardiomyocytes from within the activated adult heart after injury.”

Populations of EPDCs in the developing embryo readily differentiate into a range of specialist cells including heart muscle. However, this transforming ability has previously been thought to shut down completely in adult tissue. Scientists led by Paul  R. Riley, Ph.D., at the UCL Institute of Child Health’s molecular medicine unit, have now shown that the adult heart epicardium retains progenitor cells and that reactivating the embryonic epicardial gene Wilm’s tumor 1 (Wt1) using thymosin β4 effectively primes them to be ready for action.

Studies in experimental mice confirmed that after a heart attack, re-administration of thyomosin  β4 prompts the primed EPDCs to transform into mature cardiomycotes that migrate into the heart and integrate with existing healthy tissue to help effect repair. Compared with untreated animals undergoing a heart attack, the treated mice demonstrated improvements in functional parameters including ejection fraction and end diastolic/systolic volumes, together with beneficial changes in infarct/scar volume with increased left ventricular mass over time.

“The identification of a bona fide source of myocardial progenitors is a significant step towards resident-cell-based therapy for acute myocardial infarction in human patients,” the authors conclude. Dr. Riley points out, “Our earlier research proved blood vessels could be regenerated in adult hearts, but there were major doubts about whether the same might be true for heart muscle. This work has demonstrated a possible method for repairing hearts damaged by a heart attack and could have a major impact on future therapies to treat heart failure.”