Scientists at Albert Einstein College of Medicine of Yeshiva University have devised a way to transplant insulin-producing pancreatic cells, which causes only a minimal immune response in recipients.
The researchers believe that their work in mice may significantly influence the way type 1 diabetes is treated.
This work attains significance in view of the fact that cell transplantation therapy is currently limited, as recipients require powerful immunosuppressant medications that often result in toxic side effects and raise the risk of infection.
"Ultimately, even with immunosuppressive therapy, most of these individuals end up rejecting the transplanted cells," says the study's principal investigator, Dr. Harris Goldstein, professor of paediatrics and of microbiology and immunology at Einstein.
Describing their study in the online edition of the journal Gene Therapy, the resarchers said that the advance they made might pave the way for routine use of cell transplants as a therapy for type 1 diabetes in humans.
During the 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.
The researchers revealed that they did so by harnessing the innate ability of adenoviruses-which infect tissues that line the respiratory tract, eyes, intestines, and urinary tract-to evade the body's immune surveillance system.
They said that adenoviruses produce proteins that prevent the cells from signalling the immune system that they have been infected and should be destroyed.
According to them, 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.
Dr. Goldstein and his colleagues commenced their study with a special line of insulin-producing beta cells that were harvested from mice.
They genetically engineered those beta cells to include three adenoviral genes responsible for making immunosuppressive proteins.
The researchers said that diabetic mice that received the engineered foreign beta cells maintained normal glucose control for up to three months, while a control group of diabetic mice exhibited normal glucose control for just a few days.
"Clearly, the three proteins were not optimal, because ultimately the cells did get rejected. 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," says Dr. Goldstein.
Dr. Goldstein considers the current experiment to be a proof of concept.
"We were able to demonstrate that genetically engineered beta cells can be made highly resistant to rejection and can basically correct diabetes. This technique could conceivably be applied to protect any type of cellular transplant from rejection," he says.
The researchers admit that their approach would not be suitable to treat type 2 diabetes, in which patients have fully functional beta cells but cells throughout their body become resistant to insulin.