Each year, more people die worldwide from ischaemic heart disease than any other condition. This type of coronary artery disease is linked to a reduced blood supply to the heart.
Cardiac experts believe this type of heart disease happens because the cells that make up the heart muscle, cardiomyocytes, stop dividing and replenishing shortly after birth. A big push in research around this issue centers on creating cardiomyocytes to replace the cells failing within the heart, but because the body is no longer regenerating these naturally, they need to be developed by reprogramming other cells.
In previous studies, researchers identified successful and expedient ways to program stem cells to become cardiomyocytes, and then took another step to directly reprogram fibroblasts to create cardiomyocyte-like cells using a cocktail of cardiomyocyte-specific genes. The second method has an advantage of avoiding tumor formation, which is occasionally observed with the first method, but this method is extremely inefficient.
Looking for a new approach, University of Minnesota researchers had an interesting idea.
Hiroyuki Hirai, Ph.D., research associate, and Nobuaki Kikyo, M.D., Ph.D., associate professor, from the Masonic Cancer Center, University of Minnesota, the University of Minnesota Stem Cell Institute and Department of Genetics, Cell Biology and Development, gathered collaborators interested in testing whether or not a new fusion gene could prompt more efficient induced cardiomyocyte-like cells into production.
What they found:
- The transactivation domain of the MyoD protein is known to attract many important proteins for gene activation just like a magnet. The fusion of the MyoD domain to Mef2c, one of the introduced cardiomyocyte-specific gene, empowered Mef2c.
- The fusion gene accelerated the conversion of fibroblasts to cardiomyocyte-like cells more than 100-fold in the first two weeks.
- The maximum efficiency of the conversation was more than 15-fold higher with the fusion gene compared with the original Mef2c gene during the course of four weeks.
- The group previously showed a similar enhancement of producing stem cells from fibroblasts with the MyoD domain. This domain seems to serve as a general enhancer of cell reprogramming for the purpose of regenerative medicine.
This method of producing cardiomyocyte-like cells could make clinical care for ischaemic heart disease more effective and efficient.
You can read the whole paper, published online by the journal Cardiovascular Research.