S u m m a r y :
Mending broken hearts can now be done in laboratory through cell reprogramming, suggests a new study published in the journal Cell Reports. The research promises an unprecedented approach to heart disease therapy.
Broken Hearts Mended
Broken hearts can be mended through a simple cell reprogramming: the new research documents how ordinary cells known as fibroblasts can be transformed into new, healthy cardiomyocytes (heart muscle cells), a procedure that is hoped to be successful within diseased hearts of patients as a way to reverse heart disease in the future. Led by UNC-Chapel Hill scientists, the study also indicate molecular details that are to be used to fine tune the technique by boosting efficiency.
“From these studies we may be able to define pathways to increase the efficiency of fibroblast reprogramming,” says senior author Frank Conlon.
Fixing a ‘Heartbreak’
Heart disease is typically characterised by the blockage of coronary arteries and the gradual replacement of cardiomyocytes with scar tissue, resulting in heart function loss that can lead to heart failure. This happens, partly because the heart muscle cells are restricted in their proliferation ability, and because they do not efficiently replace themselves following damage. This is why the scientists have attempted to find ways to transform fibroblasts, a cell type abundant in the heart, into new cardiomyocytes. This procedure was found to be successful in the diseased hearts of lab mice who eventually had improved heart function.
However, this cell reprogramming therapy is not as efficient for clinical use, because of the lack of understanding of the molecular pathways behind the process, explains Conlon.
Turning Fibroblasts into Cardiomyocytes
The fibroblasts were initially exposed to a modified retrovirus whose entry into the cells led to the production of 3 key transcriptor proteins, thus modifying gene expression in the cells, such that the fibroblasts metamorphosed into cardiomyocytes within 3 days.
Conlon and his colleagues also made use of advanced techniques to trace the changes in protein levels in the fibroblasts during the reprogramming process: they analysed the concentrations of thousands of proteins in the cells during the 3 days, thereby unveiling a “carefully orchestrated series of molecular events”. For instance, 23 classes of proteins changed in abundance when the viruses entered the cells, which triggered the reprogramming after 48 hours. Another important modification constituted a sharp increase in protein Agrin level; this protein is known to be involved in repair processes in damaged hearts, and it also inhibits a signalling pathway that plays a role in the regulation of organ size. This suggests that the reprogramming of fibroblasts might be enhanced by inhibiting this pathway.
More studies will now be done to better understand how this cell transformation occurs.