In a development that could pave the way for heart tissue regeneration, US and Chinese scientists claim to have successfully used a tiny molecule that fine-tunes gene expression to stimulate the mouse heart to grow new cells.
Unlike other organs, the adult human heart lacks the ability to form new cells and repair damage after an injury such as a heart attack. Only mice have been found to renew cardiomyocytes, or heart muscle cells, for up to six days after birth.
A team led by Edward Morrisey, professor of the University of Pennsylvania, wondered if they could resurrect this regenerative potential in adult mice using a molecule called miR302-367 that drives cardiomyocyte cell proliferation during embryonic development in mammals, including humans.
They found that in newborn mice, over-expressing this molecule boosted heart muscle cell proliferation, while deleting it blunted cell growth.
Further research revealed that miR302-367 blocks genes in a signaling pathway called Hippo, which acts as a molecular brake that prevents cells from dividing.
Releasing this brake “allows cardiomyocytes to re-enter the cell cycle and begin to regrow heart muscle”, Xinhua news agency cited Morrisey as saying on Wednesday.
In adult mice that suffered an experimental myocardial infarction injury, activating miR302-367 stimulated new patches of cells to grow, resulting in reduced scar formation and increased number of heart muscle cells.
However, expressing the molecule for several months led to dangerously high cell proliferation, resulting in an enlarged heart and ultimately heart failure.
The researchers overcame this limitation by injecting a miR302-367 mimic with a short half-life into the mice.
Mimic treatment for seven days after cardiac infarction seemed to heal the injured tissues while sparing the mice of these side effects, the scientists said.
Morrisey said they will next test the new approach in a larger animal model.
The study, also involving researchers from the Temple University and China’s Fourth Military Medical University, was published in the US journal Science Translational Medicine.