A Novel Form of Gene Therapy Can Treat Diabetes With Genetically Modified Skin Transplants

“The human skin is a promising conduit for genetic engineering, as it is the largest and most accessible organ.”

 


Researchers from the University of Chicago have successfully completed a proof-of-concept study where they managed to treat obesity in mice using a new type of gene therapy that utilized skin transplants. Human skin transplantation is a well-established clinical approach that has been used for the treatment of burns. However, using it as a vehicle to deliver genetic treatments for non-skin diseases could be revolutionary. 

There are several reasons why skin stem cell therapy can be applicable to a broad type of diseases. The skin is the largest human organ, providing an easy access to cells needed for genetic treatments. The skin enables easy monitoring for potential off-target mutations resulting from the CRISPR intervention, as well as easy removal of such mutations, should they occur. Most importantly, proteins that are secreted by epidermal cells can reach the blood circulation and achieve desired therapeutic effects for the entire body. 

In the study published this month, titled Engineered Epidermal Progenitor Cells Can Correct Diet-Induced Obesity and Diabetesthe scientists genetically engineered skin cells to be able to deliver GLP1 (glucagon-like peptide 1) - a hormone which regulates blood glucose. Then they developed a surgical procedure which allowed them to successfully engraft the new skin onto a mouse host. Finally, the genetically modified cells had a mechanism for releasing GLP1, which was regulated by a small amount of antibiotic that was fed to the mice. The treated group of obese mice significantly reduced their body weight and insulin resistance, compared to the control group. 

Xiaoyang Wu, one of the authors of the study, says in an interview for ResearchGate:

 ”We established a novel mouse to mouse skin transplantation system to test skin gene therapy. […] Our proof-of-concept work demonstrated it’s possible to use engineered skin grafts to treat many non-skin diseases. Clinical translation of our findings will be relatively easy, as skin transplantation in human patients has been well established and clinically used for treatment of burn wounds for many years.”

Skin grafts are an exciting new avenue to explore for genetic treatments of diseases. They are relatively inexpensive compared to other types of gene therapy, the procedure is minimally invasive, and it has already been tested and proven safe. 

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Scientists study tattooed corpses, find pigment in lymph nodes

It turns out, that tattoo ink can travel throughout your body and settle in lymph nodes.

17th August 1973: An American tattoo artist working on a client's shoulder. (Photo by F. Roy Kemp/BIPs/Getty Images)
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In the slightly macabre experiment to find out where tattoo ink travels to in the body, French and German researchers recently used synchrotron X-ray fluorescence in four "inked" human cadavers — as well as one without. The results of their 2017 study? Some of the tattoo ink apparently settled in lymph nodes.


Image from the study.

As the authors explain in the study — they hail from Ludwig Maximilian University of Munich, the European Synchrotron Radiation Facility, and the German Federal Institute for Risk Assessment — it would have been unethical to test this on live animals since those creatures would not be able to give permission to be tattooed.

Because of the prevalence of tattoos these days, the researchers wanted to find out if the ink could be harmful in some way.

"The increasing prevalence of tattoos provoked safety concerns with respect to particle distribution and effects inside the human body," they write.

It works like this: Since lymph nodes filter lymph, which is the fluid that carries white blood cells throughout the body in an effort to fight infections that are encountered, that is where some of the ink particles collect.

Image by authors of the study.

Titanium dioxide appears to be the thing that travels. It's a white tattoo ink pigment that's mixed with other colors all the time to control shades.

The study's authors will keep working on this in the meantime.

“In future experiments we will also look into the pigment and heavy metal burden of other, more distant internal organs and tissues in order to track any possible bio-distribution of tattoo ink ingredients throughout the body. The outcome of these investigations not only will be helpful in the assessment of the health risks associated with tattooing but also in the judgment of other exposures such as, e.g., the entrance of TiO2 nanoparticles present in cosmetics at the site of damaged skin."

Photo by Alina Grubnyak on Unsplash
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