Scientists discover heart cell reprogramming process

Scientists now understand how scar tissue cells can be turned into healthy heart muscle, paving the way to precise cell reprogramming and personalized medicine.

Five years ago, University of North Carolina (UNC) researchers published a study proving that this conversion was possible, but they couldn’t explain every step of the process.

Now that they understand how this happens, the researchers are a step closer to being able to turn skin cells into muscle, and target only unhealthy cells to be reprogrammed.

According to the study authors, this discovery of how the process works will soon allow them to reprogram skin cells into cells from other organs for testing personalized medicines.

A new study has worked out the process by which cell reprogramming turns scar tissue cells (in blue) into healthy heart muscle cells (in red)

When the heart becomes damaged, scar tissue develops in the healing process, much like any other muscle in the body. This can happen in response to heart disease or heart attacks.

The scar tissue acts like dead weight. It does not contract like the rest of the heart, so it becomes a burden to the working muscle. If the heart becomes too overwhelmed by scar tissue, it can weaken the heart so much that it can no longer pump, or lead to congestive heart failure.

But Dr Li Qian at UNC and her team have shown that they can undo some of the damage.

She says that after the discovery that stem cells could be reprogrammed, scientists realized that many ‘cells are more plastic than we thought.’

She and her team developed one of the methods of using viruses to deliver gene therapies to heart scar tissue cells – called cardiofibroblasts – to turn them back into healthy heart muscle cells.

Now, they have used mathematical algorithms with their chemical and genetic modification processes to get a ‘high resolution’ view of how the process works.

Dr Qian says their simulation revealed that different cells respond differently to the reprogramming. ‘Using this technology, we are able to really tease out the possibilities of the scar-forming cells…and can tell their potential for converting [to healthy cells],’ she says.

This will enable scientists to ‘target the more potent cells…and let them focus and follow the most straightforward route.’ 

Though the UNC team used heart cells as their test, Dr Qian says that once the reprogramming process is fully understood, it can be used for other tissue cells as well.

Converting cells has implications for testing and developing personalized medicine too, she says. For example, Dr Qian says that sample skin cells, which are easy to collect, could be converted to, say, hard muscle cells, like those of the heart.

Those cells would still have an individual’s unique genetic profile, so they could be tested for how that person would respond to various drugs and treatments, without the risk of negative side effects.

For heart scar tissue reprogramming, Dr Qian says that her team’s discovery of the steps of the conversion process will help them to hone its effectiveness and efficiency.

She wants to ensure that the therapy only affects the scar tissue cells, and does not interact with healthy heart muscle cells.

‘If we have high enough efficiency, so most of the scar tissue can get converted to healthy tissue, then we can focus on other things, logistical things like how [the reprogramming genes] are delivered,’ she says.

Eventually, scientists may look for another delivery mechanism, instead of the virus they are currently using.

‘Only when we know every single step, can we really remove road blocks to each step and make the process happen more smoothly,’ she says.