Bioengineered Skin Grafts Control Blood Pressure in Mice
FRIDAY Jan. 15, 2010 -- Bioengineered skin cells can produce molecules that control blood pressure in mice, and the same technology is potentially usable against a number of medical conditions, researchers report.
"Our main interest is showing the therapeutic utility of this approach," said Dr. Jonathan Vogel, a senior investigator in the dermatology branch of the U.S. National Cancer Institute, and lead author of the report published online in this week's issue of the Proceedings of the National Academy of Sciences.
Blood pressure control was the target in the mouse experiment because "some of our collaborators on the paper have an interest in hypertension," Vogel said. The study was done in collaboration with researchers at the University of Giessen and Marburg in Germany.
The bioengineered skin cells, which were altered by using a retrovirus to insert a gene into them, were applied as grafts. "Skin grafts are relatively easy to construct," Vogel said. "The desired gene can be placed in the upper part of the skin and also in the fibroblasts, which provide the supportive structure of the skin."
Tests showed that the skin patches lowered the blood pressure of mice fed a normal diet and prevented high blood pressure in mice fed a diet high in salt.
"We used a retrovirus with RNA that makes two proteins," Vogel said. "One of the proteins is a peptide that controls and lowers blood pressure. The other can be used as a marker."
The active molecule produced by the bioengineered cells was atrial natriuretic peptide, a hormone that lowers blood pressure.
The successful trial is just a first step in what promises to be a long road to the use of skin grafts in medicine, Vogel said.
"It is one thing to do it in a mouse," he said. "The question is whether it can be scaled up to use in larger animals. That question still has to be answered."
Other questions are the duration of the effect (because as Vogel noted, "these were fairly short-term studies"), and how many other conditions the technique might be used to treat.
"One other condition we are talking about is anemia," Vogel said. "That has been actively thought of in our laboratory. But that is far in the future. It would require much tighter regulation than we now can achieve."
And while this was "a first step in a small animal model," a point has been proven, he added.
"It shows we can engineer a skin graft, can graft it successfully, and that the product that the skin cells make gets access to the bloodstream, which is not trivial. It gets there in sufficient levels to have a biological effect," Vogel said.
Dorothy Supp, an associate investigator at Shriner's Hospital for Children in Cincinnati and adjunct research professor in the University of Cincinnati's department of surgery, who has her own research project using modified skin cells, called the new study "very exciting."
"My work involves generating modifications in skin cells to improve healing," Supp said. Like Vogel, she uses a retrovirus to modify the cells. "What we would like to do is increase the expression of beneficial genes and decrease the expression of harmful ones," she said.
Skin graft therapy is nearing medical application after 20 years of effort, Supp explained. "The skin is a model system for gene therapy, and the fact that you can put a small graft on an animal and get a systemic response is very exciting," she said.
The U.S. National Library of Medicine has more on skin grafts.
Posted: January 2010