A study has created new healthy heart muscle cells within a patient's own ailing heartScientists have reprogrammed ordinary cells called fibroblasts into new and healthy heart muscle cells and recorded changes that appear to be necessary for this reprogramming. The reprogrammed ordinary cells called fibroblasts into new and healthy heart muscle cells and recorded changes that appear to be necessary for this reprogramming. The study was published in Cell Reports.

Scientists hope to reverse heart disease one day. Today, a new study led by UNC-Chapel Hill researchers reveals key molecular details that should be useful in developing this ambitious approach. "From these studies, we may be able to define pathways to increase the efficiency of fibroblast reprogramming," said senior author Frank Conlon.

Heart disease kills more than 600,000 people each year in the United States alone and remains the leading cause of death for both men and women. It typically arises from the narrowing or blockage of coronary arteries and involves the progressive replacement of heart muscle cells with scar tissue leading to a loss of heart function and ultimately heart failure.

This progressive disease process occurs in part because cardiomyocytes have a very limited ability to proliferate and replace damaged heart muscle. Scientists, therefore, have been experimenting with techniques to transform fibroblasts collagen-making cells that are abundant in the heart of new cardiomyocytes. They have shown that they can make this therapeutic cell-reprogramming process work in the diseased hearts of lab mice and thereby improve heart function.

First, they triggered the reprogramming using a technique based on one Qian developed in 2012. They exposed fibroblasts to an engineered retrovirus that enters the cells and starts producing three key "transcription factor" proteins, which effectively reprogram gene expression in the cells, causing the cells to turn into cardiomyocytes within a few days. The researchers examined the levels of thousands of distinct proteins in the cells during the three-day transformation from fibroblasts to cardiomyocytes

Future studies will determine which of these myriad changes does indeed drive reprogramming, and more importantly which changes can be enhanced to improve reprogramming efficiency. This finding one of the hundreds of individual clues generated by the study raises the possibility that inhibition of Hippo signalling is needed for cardiomyocyte reprogramming.

The data suggest that the reprogramming process kicked off at about 48 hours after the viruses entered the fibroblasts and significantly affected the abundance of 23 classes of protein. One of the most striking changes was a sharp rise in the level of a protein called Agrin, which has been found to promote repair processes in damaged hearts. Agrin also inhibits another signalling pathway called the Hippo pathway, known to be involved in regulating organ size.