Skin Cells Reprogrammed to Embryonic Cells then Turned Into Heart Cells

Scientists turn skin cells to embryonic state, then to heart cells

Feb 13, 2009
Milwaukee Journal Sentinel
Mark Johnson
Feb. 13, 2009

In work that extends science's power to alter the basic unit of a human being, researchers at the University of Wisconsin-Madison have taken skin cells that were reprogrammed back to their embryonic origin and grown them into functional, pulsing heart cells.

Moreover, the human heart cells grown using this technique were very similar to those grown from embryonic stem cells, the scientists reported Thursday in the journal Circulation Research.

Timothy Kamp, co-director of UW's Stem Cell and Regenerative Medicine Center and one of the authors of the new paper, said the reprogrammed heart cells made in the laboratory performed some key functions of the heart cells inside our bodies. They generated electrical pulses, and in response to these pulses, they contracted. It is the collective contraction of all these cells that enables the heart to beat.

"This is a proof-of-principle experiment, but it's not ready for prime time," Kamp said, cautioning that such manufactured heart cells are not yet safe for use in humans.

The cells, called cardiomyocytes, had once been skin cells. To turn cells from skin to heart, scientists first sent them back to the embryonic state by infecting them with viruses carrying genes, a method that could cause cancer.

Still, the reprogrammed cardiomyocytes offer researchers an immediate tool for studying heart diseases in a lab dish and testing drugs against them.

"This is probably the most exciting short-term application," said Christine Mummery, a professor of developmental biology at Leiden University Medical Center in the Netherlands, in an e-mail. She was not involved in the research.

No embryo needed

The new paper adds to a growing body of evidence suggesting that scientists can now obtain cells that perform just like embryonic stem cells without destroying a human embryo. Since teams led by James Thomson at UW and Shinya Yamanaka at Kyoto University showed in 2007 that human skin cells could be returned to the embryonic state, researchers have sought to determine whether the new technique can be used to make all of the more than 200 cell types in the body.

This versatility is one of the crucial powers of an embryonic stem cell, offering modern medicine a potential repair kit for illnesses such as Alzheimer's, diabetes and heart disease. In the last year, scientists have used reprogramming to make blood cells and motor neurons, the cells that transmit nerve impulses and make muscles contract.

"This is another piece of evidence to say, 'So far, so good,' but we still have a long way to go," Kamp said. "This is going to take time and multiple different investigators looking at multiple different cell types."

"I think this is highly important, so important that we had asked the same question," said John Lough, a professor and stem cell researcher at the Medical College of Wisconsin, who had been working independently on a similar project. "We've seen the beating heart cells here."

Similar technique used

Lough and two other Medical College researchers, Stephen Duncan and Ana Sepac, have also been trying to grow reprogrammed cells into heart cells and have succeeded using a different method than the one employed by Kamp's team at UW. Nonetheless, Lough declared himself delighted with the UW paper, saying it strengthens the case for a future study he has been planning.

Researchers at the Medical College and Children's Hospital of Wisconsin hope to use the reprogramming method to study congenital heart disease in children and have submitted a grant request for the project to the National Institutes of Health. They're particularly interested in hypoplastic left-heart syndrome, a condition that leaves newborn babies with an underdeveloped left side of the heart. The condition is fatal unless surgically corrected.

Genta Narazaki, a stem cell researcher at Kyoto University's Institute for Frontier Medical Sciences (OOTC:MCLS) , said the UW work "has great meaning," and should pave the way for studies that will help researchers better understand heart disease.

In the last year, scientists have collected and reprogrammed skin samples from patients with spinal muscular atrophy and Lou Gehrig's disease, turning the cells into motor neurons in order to study the illnesses in a lab dish. This technique can now be extended to heart disease.

"I think many groups are doing it right now," Mummery said. "We are."