Researchers engineer pancreatic cell transplants to evade immun...(rris Goldstein M.D. professor of pediatr...)

In this study, Dr. Goldstein and his colleagues devised a way to make foreign beta cells invisible to a transplant recipient's immune system, dramatically protecting them from rejection. They did so by harnessing the innate ability of adenoviruses to evade the body's immune surveillance system. (Adenoviruses infect tissues that line the respiratory tract, eyes, intestines, and urinary tract). After infecting cells, adenoviruses produce proteins that prevent the cells from signaling the immune system that they have been infected and should be destroyed. The viruses also produce proteins that can turn off a cell's built-in self-destruct mechanism, which is usually triggered when something disturbs a cell's internal functions.

The researchers began with a special line of insulin-producing beta cells, developed at Einstein, that were harvested from mice. When injected into diabetic mice, these foreign cells can restore normal glucose control, but only temporarily. The transplanted cells are soon destroyed by the mouse's immune system and glucose levels begin to rise, returning to pre-transplant disease levels.

Dr. Goldstein and his colleagues genetically engineered these beta cells to include three adenoviral genes responsible for making immunosuppressive proteins. Diabetic mice that received these engineered foreign beta cells maintained normal glucose control for up to three months. In contrast, a control group of diabetic mice that received the regular foreign beta cells exhibited normal glucose control for just a few days.

"Clearly, the three proteins were not optimal, because ultimately the cells did get rejected," says Dr. Goldstein. "We are now looking at other viral genes that also contribute to immune suppression and are trying to identify the best gene combination to use."

Dr. Goldstein views the current experiment a
'/>"/>