Researchers from the University of California, San Francisco, and Indiana University School of Medicine managed to reprogram heart scar tissue cells in mice into working heart muscle cells. The groundbreaking achievement, published in the online edition of Nature, paves the way for future regeneration techniques.
Research leaders Li Qian, Ph.D., and Deepak Srivastava, M.D., of San Francisco University used gene-splicing techniques to insert three genes into fibroblast cells, i.e. structural cells not directly involved in the heart’s pumping function, whose activity subsequently provoked some of the fibroblast cells to become cardiomyocytes, i.e. cells that comprise cardiac muscle.
Dr. Simon J. Conway, Ph.D., professor of pediatrics and director of the Program in Developmental Biology and Neonatal Medicine at the Herman B Wells Center for Pediatric Research at the IU School of Medicine, explained that their study used an experimental mouse strain, that allows researchers to mark and follow the development of fibroblast cells over time.
He continued, saying:
“Not only do the reprogrammed cells express everything that a cardiomyocyte should, they can actually show that they have a mature contractile apparatus so they can contract like a normal cardiomyocyte and that they are electrically coupled to their neighbors, because they have to all contract in unison to have a strong heartbeat.”
The researchers refer to the fact that heart failure is a leading cause of death, and point out that unlike muscle cells in other parts of the body, cardiomyocytes cannot be regenerated and repair damage caused by a heart attack.
Heart injury causes an excessive amount of fibroblasts cells at the site of the damage. This leads to a buildup of scar tissue that replaces the cardiomyocytes. With the use of gene therapy techniques that involves retroviruses, the researchers inserted the genes into the fibroblast cells, which in turn enabled the production of proteins that are vital for the development of the heart and muscle, particularly in embryos.
According to the researchers, about 10% of the fibroblasts showed proof of reprogramming and started to work as cardiomyocytes. They added that the treatment also decreased the size of the damaged heart tissue and led to improved heart function.
Dr. Conway said that although the researchers of the University of California had previously reported success in reprogramming the fibroblast cells in tissue culture in the laboratory, using Paige Snider’s IU School of Medicine mouse model was vital in order to provide evidence of their success in a living system.
He said:
“Working in a dish is great, but if you can get it working in an animal model and it can form normally functioning cardiomyocytes that don’t become tumors, that are stable and integrated into the rest of the cardiomyocytes, that’s important.”
Written By Petra Rattue