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 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," Dr. Wu said. "It took us a few years to optimize our 3D skin organoid culture system." This study, entitled "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," Dr. Wu said. "This is exciting for us." The article is open-access.
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