A team of scientists from the University of Chicago has succeeded in using CRISPER gene editing technology to develop a removable patch of genetically edited skin cells to treat type-2 diabetes in mice.
The researchers edited skin stem cells from newborn mice to stimulate the release of glucagon-like peptide 1 (GLP-1) when manually induced. The team also recreated the same test using human skin cells and achieved positive results.
"We didn't cure diabetes, but it does provide a potential long-term and safe approach of using skin epidermal stem cells to help people with diabetes and obesity better maintain their glucose levels," stem cell biologist and senior author Xiaoyang Wu clarifies.
How The Gene-Edited Mice And Human Skin Cells Work
The proof of concept study published in the journal Cell Stem Cell on Aug. 2, aimed to show that editing genes and applying them as skin grafts to treat medical conditions could work on animals.
The researchers noted that using removable patches of gene-edited skin is also less risky than other gene therapies since skin grafts are not invasive and could also be used in the long term.
In order to prove this, the team used CRISPR to engineer mouse skin cell grafts that would regulate blood-glucose hormones when applied to diabetic mice with healthy immune systems. The patch carried a mutated gene that extends GLP-1's half-life and allows it to circulate in the bloodstream longer. They also attached an inducible promoter that would serve as a switch to increase production of GLP-1 by exposing it to the antibiotic doxycycline.
GLP-1 is the hormone responsible for stimulating the pancreas to produce insulin, which helps manage the body's blood sugar levels.
Treating Diabetes In Mice With Skin Grafts
To test whether the patch worked or not, the team fed the skin-grafted, wild-type mice with very small amounts of doxycycline. Tests showed that the patch successfully released dose-dependent levels of GLP-1 in their bodies.
The next step was to feed both healthy and diabetic mice with a high-fat diet to induce obesity and potentially increase their blood glucose levels. The team then noted that the said groups rapidly gained weight. However, when doxycycline was introduced, the skin-grafted mice gained less weight than their normal, healthy counterparts.
When the mouse-skin-grafted mice switched to human skin grafts, the mice surprisingly did not reject them and similar results were also achieved. The skin grafts were able to function properly for over four months and the team is looking into how much longer it can be used.
"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," Wu expressed.
The team is now in the middle of monitoring whether the immune reaction to GLP-1 would develop in the mice, as well as looking at the possibility of using the technique for treating genetic diseases and other metabolic conditions.
