Skin cells have been exposed to molecules that reverse their development but still retain their function, creating a kind of stem cell that keeps its original function in the body
8 April 2022
Researchers have developed a method that can turn back the biological clock on skin cells by 30 years, creating stem cells from mature ones, which could be used to treat skin conditions in the future.
In 2007, Shinya Yamanaka at Kyoto University in Japan developed a technique that could transform adult skins cells into stem cells by inserting four specialist molecules, dubbed “Yamanaka factors”, that reverse cell development. It takes around 50 days of exposure to these molecules for normal cells to be reprogrammed into what are known as induced pluripotent stem cells (iPSCs).
“When you turn to a cell into an iPSC, you lose the original cell type and its functionality,” says Diljeet Gill at the Babraham Institute in Cambridge, UK.
Gill and his colleagues have now devised a technique that uses Yamanaka factors to rejuvenate skin cells without losing their previous functionality.
The researchers collected skin cell samples from three human donors that had an average age of around 50, then exposed these to the Yamanaka factors for just 13 days to partially anti-age the cells. They then removed the Yamanaka factors and left the cells to grow.
As we age, our DNA gets tagged with chemicals, so tracking these markers can help us determine how old our bodies are. This is known as our epigenetic clock. Over time, some of our genes will either turn on or off, the collection of which is known as the transcriptome.
Gill and his team found that the epigenetic clock and transcriptome profiles of the partially reprogrammed cells matched the profiles of skin cells that belonged to people who were 30 years younger.
The rejuvenated cells also functioned like younger ones, too, creating more collagen than those that didn’t undergo reprogramming. And when placed onto an artificial wound, the reprogrammed cells moved to close the gap much quicker than the older ones did.
“In young people, if you cut yourself, it’ll take quicker to heal the wound, while it would take me longer to heal,” says team member Wolf Reik, also at the Babraham Institute. “It’s very exciting – not only the molecular read-outs that are younger, but the cell also functions more like young cells.”
The key advance in this study is that we are now able to substantially rejuvenate cells without changing their identity or functionality, says Reik. “In previous studies, you would end up with a stem cell, which is not what you’d want for therapy.”
The technique may one day be useful in treating skin conditions, such as burns and ulcers. There is also the added bonus that the cells wouldnt be rejected by an individual’s body, because they would be their own cells, says Gill.
“So far, we’ve only tested this technique in skin cells. We’re excited to see if we can translate it across other cell types,” says Gill.
Journal reference: eLife, DOI: 10.7554/eLife.71624
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