Researchers from New York's Yeshiva University have announced a genetic engineering technique that protects transplanted insulin-producing islet cells from immune response and rejection for up to three months in mice recipients.
At present, the widespread use of cell transplantation therapy is limited because of a lack of donors, and because transplant recipients are forced to take powerful immunosuppressant drugs that have toxic side effects and raise the risk of infection.
Led by Professor Harris Goldstein, the researchers genetically engineered insulin-producing beta cells from mice to produce three immunosuppressive proteins to help them avoid detection by the immune system once transplanted into the recipient mice.
Immune-suppressing proteins used to ‘hide’ beta cells
Initially, the researchers found that when beta cells were modified to produce the viral ‘gp19K’ protein, they expressed 90% fewer ‘class I major histocompatibility complex (MHC)’ molecules on their cell surface. MHC molecules normally present proteins from within the cell to the immune system, and in Type 1 diabetes this process is thought to activate the immune attack against beta cells. Another viral protein, RIDá/â, inhibited the beta cells’ production of a receptor that can initiate cell death, called ‘Fas’, by over 75%.
Glycaemia remained normal for up to three months
When mice with diabetes were injected with the modified beta cells, normal glucose control was achieved for up to three months before the cells were rejected. Beta cells that had not undergone the modification were rejected within a few days, it was reported in the journal Gene Therapy.
Proof of concept, rather than breakthrough
Dr Iain Frame, Director of Research at Diabetes UK, said that the results should be treated as a 'proof of concept' rather than a breakthrough, and that procedures using this method remain a long way off.
"The effect on the blood glucose levels of the mice was transient and, as admitted by the lead researcher, the transplanted cells were soon rejected," Dr Frame continued.
"To say that the results of this study move us closer to a cure for Type 1 diabetes would unnecessarily raise the expectations of people with the condition."
The researchers are now looking at other viral genes that also contribute to immune suppression and are trying to identify the best gene combination to use in further studies.