Artificial skin transplants could help treat diabetes

Barsaba Taglieri
Agosto 4, 2017

And they believe the general concept could someday be used to treat various diseases.

A new form of gene therapy administered through skin transplants can help improve treatments for Type-2 diabetes and obesity, researchers have claimed. This is the hormone that stimulates the pancreas to produce insulin while maintaining healthy levels of blood glucose. About 80% of the engineered skin grafts successfully transplanted onto a small spot on each mouse host's back and began secreting GLP-1 upon the appropriate induction cue.

Xiaoyang Wu, a stem cell biologist at the University of Chicago, led the "proof of concept" study.

"Overall, I think it's a very neat solution to this problem here of delivery of GLP-1 for the treatment of type 2 diabetes and obesity", says Jeff Millman, a biomedical engineer and stem cell researcher at Washington University in St. Louis, who was not involved in the study. "We focus on diabetes because it's a common disease, but this is a potential strategy to treat a range of metabolic and genetic conditions".

But Dominguez-Bendala also pointed to what's "cool" about the experiments.

"This is really flexible", Wu said, "We can use the skin as a platform to develop all sorts of new therapies".

The CRISPR method of gene editing has shown a great deal of promise for quickly and precisely "editing" patches of DNA.

Before CRISPR, scientists could not control where an inserted gene would be integrated into the genome.

Wu and colleauges used CRISPR to make specific edits in GLP1, including one that allowed the gene to be turned "on" or "off" as needed, by using the antibiotic doxycycline.

An immunofluorescence image of one of the engineered skin graftsXIAOYANG WU ET AL.

Building on 40 years of skin transplant knowledge, the team looked at ways to genetically modify epidermal progenitor cells to see if they could be transplanted into an organism and deliver a targeted gene therapy. In turn, the animals' insulin levels rose and their blood sugar dipped. When fed a high-fat diet, the mice gained weight and became obese. They also showed less resistance to the effects of insulin, and lower blood sugar levels.

"We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems", said Xiaoyang Wu, assistant professor at the University of Chicago in the US.

For instance, he said, skin cells could be engineered to provide an essential protein that is missing because of a genetic defect.

For example, hemophiliacs lack the necessary protein for clotting blood.

Skin cells could be an ideal way to deliver such therapies, Wu said. For one, the system is well established. Since the 1970s, doctors have known how to harvest skin stem cells from burn victims, then use those cells to create lab-grown skin tissue.

Dominguez-Bendala agreed that using skin cells has advantages. A skin graft therapy could potentially introduce the needed protein into the blood stream. And research in animals doesn't always pan out in humans. GLP1 also reduces appetite, and so prevents weight gain.

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