Scientists at the University of Chicago genetically modified skin cells to produce glucagon-like peptide 1 (GLP1) protein that is beneficial in diabetes and reduces appetite, and these investigators grew the cells in a dish to form a skin graft. The grafts could potentially be used to treat diabetes and obesity, and could provide a new way to perform gene therapy for a variety of diseases.
When normal and gene-altered mice ate the high-fat diet — along with varying levels of doxycycline to induce GLP1 release — mice expressing GLP1 (left) gained less weight gain while normal mice (right) grew fat. Credit: Wu Laboratory, the University of Chicago
Doctors have been able to remove skin stem cells from burn patients and grow skin grafts in the lab since the 1970s. However, in this study, recently published in journal Cell Stem Cell, the researchers grew mouse skin cells to provide skin grafts for mice, as a “proof of concept,” with the idea that the technique might also be applicable to humans.
They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates insulin secretion from the pancreas, into the skin cells. Stimulating insulin production is useful in treating diabetes, but GLP1 can also reduce appetite, and so could help to treat obesity. The genetically-modified skin cells grew into skin grafts in the lab, and the researchers then grafted them onto mice.
The scientists fed the gene-altered or normal mice a high-fat diet. Both types of mice gained weight and became obese rapidly. However, when the researchers included a substance in the feed to activate the GLP-1 gene in the skin graft, only the normal mice grew fat and the GLP1 mice didn’t put on as much weight. The GLP1 mice also showed reduced glucose levels in response to the insulin simulating effect of GLP-1.
The technique could also be useful in humans, and for other types of gene therapy. “We think this technique can provide a long-term safe option for the treatment of many diseases,” said Xiaoyang Wu, assistant professor at the University of Chicago, and an author on the study. “It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia.”
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