Reprogramming helped to reduce the scar tissue size and improve heart functioning in mice

Scientists have found an easier way of repairing hearts damaged by cardiac arrest — reprogramming one kind of heart cells into another. A paper published today (April 19) in Nature details how the remarkable feat of reprogramming cardiac fibroblasts into adult cardiac muscle-like cells (cardiomyocyte) produced promising results.

A few years ago, researchers introduced stem cells directly into the heart and saw some improvement in heart functioning. With further progress, scientists were able to reprogram adult heart cells into pluripotent cells in the lab and inject them into the heart.

A step further

Deepak Srivastava of the University of California and his team went a step further and reprogrammed cardiac fibroblasts into adult cardiac muscle-like cells in the lab.

But in the work reported today, Dr. Srivastava and his team were able to change (reprogram) the cardiac fibroblasts into adult cardiac muscle-like cells inside the body of mice.

This was accomplished by injecting three transcription factors directly into the heart. Behold, the cardiac fibroblasts, which make up nearly 50 per cent of the heart cells, reprogrammed into heart muscle-like cells.

Significant changes were seen three months after the researchers induced heart damage in the mice and the transcription factors were introduced.

Significantly improved

“The fraction of blood ejected with each ventricular contraction (ejection fraction), the volume of blood ejected (stroke volume), and the total cardiac output per minute were significantly improved” in the mice, they write. The most significant being the “stroke volume and cardiac output,” they note.

It is not difficult to find out why the mice with damaged hearts showed an improvement in cardiac functions — ejection fraction and stroke volume.

Shrinking scar area

The researchers found the scar area (damaged heart cells) shrinking in size eight weeks after the transcription factors were directly introduced into the hearts of the mice. Shrinkage of the scar tissue is proof that the damaged heart muscle cells were healing.

It was once thought that heart muscle cells once damaged after a heart attack (due to lack of oxygen) turn into scar tissue, and can never be healed. Scar tissue reduces the heart's pumping ability.

They also found a “significant increase” in vascular density in the “border zone of reprogrammed hearts at eight weeks.”

One more important observation was that the initial reprogramming efficiency was the same as that obtained in the lab. Also, the cardiac fibroblasts were “more fully reprogrammed” into heart muscle cells and “more closely resembled endogenous cardiomyocyte [heart muscle cells] than their cultured counterparts,” they write.

“The ability to regenerate adult heart tissue from endogenous cells is a promising approach to treating cardiac disease that may face fewer obstacles to clinical translation than other approaches,” they write. “Conducting trials in large animals will be important to refine the technology and assess its safety and efficacy.” The next logical step is to achieve the same level of success in large animals.