A research team based at the University of Chicago has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases.

In the August 3, 2017 issue of the journal Cell Stem Cell, the researchers provide “proof-of-concept.” They describe a new form of gene-therapy — administered through skin transplants — to treat two related and extremely common human ailments: type-2 diabetes and obesity.

“We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems,” said study author Xiaoyang Wu, PhD, assistant professor in the Ben May Department for Cancer Research at the University of Chicago. “We think this platform has the potential to lead to safe and durable gene therapy, in mice and we hope, someday, in humans, using selected and modified cells from skin.”

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patient’s wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

“The mouse system is less mature,” Wu said. “It took us a few years to optimize our 3D skin organoid culture system.”

This study, “Engineered epidermal progenitor cells can correct diet-induced obesity and diabetes,” is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. “We have a better than 80 percent success rate with skin transplantation,” Wu said. “This is exciting for us.”

They focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

The researchers inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive and inexpensive.

There is also a need. More than 100 million U.S. adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than 2 out of 3 adults are overweight. More than 1 out of 3 are considered obese.

More details at https://www.sciencedaily.com/releases/2017/08/170803122728.htm

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