In mammals, including humans, the cells that contract the heart muscle and enable it to beat don’t regenerate after injury. After a heart attack, there is a dramatic loss of these heart muscle cells and those that survive cannot effectively replicate. With fewer of these contractile cells, known as cardiomyocytes, the heart pumps less blood with each beat, leading to the increased mortality associated with heart disease.

Now, researchers at the University of Pennsylvania’s School of Engineering and Applied Science and Perelman School of Medicine have used mouse models to demonstrate a new approach to restart replication in existing cardiomyocytes: an injectable gel that slowly releases short gene sequences known as microRNAs into the heart muscle.

Though the reasons cardiomyocytes don’t regenerate aren’t fully understood, the researchers used microRNAs that target signaling pathways related to cell proliferation, and were able to inhibit some of the inherent ‘stop’ signals that keep cardiomyocytes from replicating. This resulted in cardiomyocytes reactivating their proliferative potential.

With more heart cells dividing and reproducing, mice treated with this gel after heart attack showed improved recovery in key clinically relevant categories.

The study was led by Edward Morrisey, Professor in Medicine, member of the Cell and Molecular Biology graduate group and Scientific Director of the Penn Institute for Regenerative Medicine in Penn Medicine; Jason Burdick, Professor in Bioengineering in Penn Engineering; Leo Wang, a graduate student in Burdick’s lab; and Ying Liu, a post-doctoral researcher in Morrisey’s lab.

It was published in the journal, Nature Biomedical Engineering.

More than a potentially life-prolonging treatment itself, the researchers see this microRNA-gel approach as representing a new, more direct avenue for precision regenerative medicine.

‘We’re seeing a change in approaches for regenerative medicine, using alternatives to stem cell delivery,’ Burdick said.

‘Here, instead of introducing new cells that can have their own delivery challenges, we’re simply turning on repair mechanisms in cells that survive injury in the heart and other tissues.’

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