In a cutting-edge work by scientists at the University of Chicago Medical Center, genetically modified skin grafts was demonstrated to protect mice from developing diabetes, suggesting the technique may also be helpful to people with the condition.
Type 2 diabetes comes about due to a lack of insulin, also known as insulin resistance. Glucagon-like peptide 1 (GLP1) is a hormone which decreases appetite and helps regulate blood sugar levels by triggering the release of insulin, which removes excess glucose from the blood. However, the hormone only works for a short period. Therefore, the scientists lead by Xiaoyang Wu used CRISPR gene-editing to alter the GLP-1 gene so it would make a hormone that is active in the blood for longer.
The team then inserted this gene into mouse skin cells in a dish, and developed them into skin grafts that could be transplanted onto mice, letting the modified hormone get into their blood.
The grafts were given to mice that were fed a high-fat diet. These mice went on to gain around half as much weight as those not given grafts, and developed less resistance to insulin. High insulin resistance is a common precursor to type 2 diabetes. The researchers gained similar results when they made the grafts out of
human skin and transplanted them onto hairless mice.Around 80 percent of the grafts successfully released the edited hormone into the blood, regulating blood glucose levels over four months, as well as reversing insulin resistance and weight gain related to a high-fat diet.
“This paper is exciting for us because it is the first time we show engineered skin grafts can survive long term in wild-type mice, our proof-of-concept work demonstrated the possibility for using engineered skin graft for treatment of many non-skin diseases,” Wu said. “Clinical translation of our findings will be relatively easy as skin transplantation in human patients have been well established and clinically used for many years. It is also a very versatile platform. The engineered skin grafts can be used to release many different therapeutic molecules, and the technique can be used for treatment of many other diseases, such as genetic disorders, including urea cycle disorders and hemophilia.”
The study appears in the journal Cell Stem Cell. And owing to innovative diabetes projects like this, hopefully we are not too far from finding a more permanent way to improve life for millions of adults who suffer from diabetes worldwide.
