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Chemicals Can Reprogram Skin Cells To Act Like Heart And Nerve Cells

Sam Lemonick
This article is more than 5 years old.

A new discovery could lead to medicines that repair damage to the heart and nervous system by reprogramming our own cells to play new roles. And the potential therapy doesn't rely on stem cells or gene therapy, promising new areas of biomedical research with a lot of kinks yet to be worked out.

Cardiomyocytes are the muscle cells in your heart that pump blood out to the rest of your body. They’re precious not just because they keep you alive, but because they aren’t easily replaced. Until 2009 scientists weren’t even sure we could grow new ones, unlike most cells in our bodies. When you die, something like half of your cardiomyocytes will probably be the ones you were born with.

That’s one reason heart attacks are so dangerous. Cardiomyocytes can die when blood flow to the heart is blocked. If that happens, the heart tissue is usually gone for good.

Stem cells are often the first thing that comes to mind when scientists and doctors talk about regrowing damaged tissue, especially tissue in the heart or nervous system that doesn't easily regrow on its own. Stem cells' ability to differentiate into almost any type of cell make them a potentially powerful tool for healing, although researchers are still working out how to use them therapeutically.

New research reveals a different possible path. Sheng Ding and colleagues report in this week’s Science a way to chemically reprogram some of the body’s most abundant cells to act like cardiomyocytes. They did the same with brain cells too, research they describe in Cell Stem Cell.

Previous attempts to reprogram cells have introduced new genes to cells to change their behavior, called gene therapy. But the new method uses chemicals instead, an approach more like the drugs we take today.

Ding, a pharmaceutical chemist at the Gladstone Institutes in San Francisco, started with fibroblasts, cells that give structure to the connective tissues that support and surround organs and muscles. Fibroblasts, cardiomyocytes and almost all other types of cell in the body carry the same genetic code, no matter their function or appearance. What makes them different is what genes are expressed and how.

The researchers screened hundreds of chemicals known to affect a cell’s genetic material in some way. Some ready the chromosome, which contains our DNA, to accept new instructions. Others activate or inhibit enzymes and proteins to change the way the cell looks and acts.

By trial and error they narrowed that field to a cocktail of nine chemicals that together turned fibroblasts from human foreskin into cells that act like cardiomyocytes. After bathing in the chemicals for a few weeks, 97% beat like heart cells, and molecularly they looked like cardiomyocytes, not skin fibroblasts.

The researchers also implanted their chemically induced cardiomyocyte-like cells into mice with damaged hearts. After two weeks, they found the implanted cells had begun to grow new muscle tissue in areas where the mouse’s heart cells had died.

In a closely related project, Ding’s group used a different set of chemicals to transform fibroblasts into cells that act like neural stem cells. When implanted, they spontaneously differentiated themselves into individual types of nerve cells and proved able to self-replicate.

The cardiomyocyte-like cells show promise for growing new heart tissue, but Ding cautions that his group hasn’t managed to turn fibroblasts into fully mature cardiomyocytes. The cells they reprogrammed still had a few genetic differences with true cardiomyocytes. He thinks more time in a Petri dish or implanted in living heart tissue could bring them to maturity. Perfecting that would bring the potential therapy closer to being ready for clinical trials.

The ultimate goal, however, isn’t implanting modified cells in a damaged heart. What Ding really wants, he says, is to “develop the right cocktail of chemical drugs and delivery method that can induce heart muscle regeneration in situ.” In other words, the chemicals could convert fibroblasts that are already in the damaged heart. No surgery needed.

Song Kunhua, who researches heart tissue regeneration at the University of Colorado, is excited about the research. “That Ding et al. used small molecules to convert human fibroblasts into beating cardiomyocyte-like cells is great,” he says in an email. But like Ding, he looks forward to seeing whether the technique can convert fibroblasts inside the body.

One obvious question is, if chemicals can convert fibroblasts into other types of cells, could they be reprogrammed to grow an entire organ? Ding is cautious in answering. “Potentially,” he says. “It would require stepwise induction using different cocktails at different stages of organ development.” Figuring that out is still probably years away.

