Genetically modified skin grafts may aid in treatments for obesity and drug abuse

January 8, 2019

Stem cells have long been of interest to researchers. Relatively easy to grow in culture, stem cells can be used to learn more about diseases and to test new drugs for safety and effectiveness. Stem cells can also be used in regenerative medical techniques where healthy cells are created to repair or replace damaged tissues. 

At the University of Chicago, assistant professor Xiaoyang Wu is part of a research team in the Ben May Department for Cancer Research that is taking stem cell research in a new direction. 

“We want to take advantage of this well-established system to see if we can make ‘smart skin',” Wu explained.

The research project began in 2017. Using CRISPR-based technology, a tool that allows new genes to be introduced into cells without affecting other genes, Wu and his colleagues were able to edit stem cells in mice through a skin grafting process. The edited grafts increased insulin secretion in the mice and reversed weight gain from a high-fat diet, as well as overturned insulin resistance. As a result, progress has been made in developing a new gene therapy treatment that may eventually be used to fight diabetes in humans.

In 2018, a similar technology was applied to a study focused on preventing cocaine addiction and overdose. When testing on mice, researchers inserted an edited gene into skin cells containing the engineered enzyme butyrylcholinesterase (BChE), which breaks down cocaine. The researchers then used a grafting process to apply the edited piece of skin onto the mice. Mice that were treated with the gene were less likely to return to environments previously associated with cocaine use. Additionally, mice who received the edited skin graft were protected from cocaine overdose. Mice that had high doses of cocaine administration and were left untreated had a 100% mortality rate. This research indicates that edited skin grafts may eventually aid in suppressing cocaine addiction in humans and also reduce cocaine levels within people’s systems, preventing possible overdoses.

Skin graft transplants have been used for many years in the treatment of burn victims and individuals with certain types of skin disorders. The treatment is cost-effective compared to other alternative therapies and is known to be safe and long-lasting. In both research experiments, skin patches remained intact in the mice for a period of 10 weeks. However, because humans have much longer lifespans than mice, Wu and his team think the skin patches will be permanent in humans and will not lose their effectiveness over time.

Human clinical trials of these two genetically modified stem cell therapies are still a ways off, but Wu hopes the same technology can eventually be applied to treating other diseases and offer more cost-effective options for patients.

“Other genetic diseases can potentially be treated by engineered skin grafts,” Wu said. “Hemophilia is one example. Currently, treatment for the disease costs up to $250,000 per year because the protein is so expensive to treat. Skin patches may be just as effective and will be much more affordable.”

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