A specialist team at Dublin City University is working towards devising a new, more effective form of transplanting insulin cells, writes Dick Ahlstrom
Cell transplants hold promise as a way to end the daily insulin injections needed to keep diabetics alive. Advanced research under way at Dublin City University aims to make this promise a reality.
Dr Lorraine O'Driscoll leads DCU's Diabetes Research Group, based in the university's National Institute for Cellular Biotechnology (NICB). Her group is pursuing a range of research initiatives all directed towards the transplantation of insulin-producing cells as a way to eliminate or reduce the need for injected insulin.
"The only therapy for Type I diabetics is insulin injections. They save lives but have serious limitations," says O'Driscoll.
One alternative therapy being used to a limited extent is full pancreas transplantation. The pancreas contains beta cells, the cells that produce insulin as a way to control glucose levels in the blood.
"Full organ transplants are possible but the transplant surgeon at Beaumont, Mr David Hickey, says that of the 80 to 90 pancreata donated each year only about 10 are suitable for transplant," O'Driscoll explains. The others are "wasted" because of a failure to get a good tissue match between donor and recipient.
O'Driscoll's work could end these difficulties. She is studying procedures used to isolate, preserve and then transplant not the whole organ but only the islets of Langerhans, clusters of pancreatic cells that hold the insulin producing beta cells.
Islet transplants have been pioneered at the University of Miami, she says. She spent time in Florida studying the techniques developed there before returning to DCU. "We plan to establish the first human islet isolation unit in Ireland," she explains.
She now leads research that is progressing on a number of fronts, starting with the isolation of islets from donated pancreata.
"The islets that contain the beta cells that make insulin only represent 2 to 3 per cent of the whole organ," she says. Only about 40 per cent of these islets can be recovered using the current best techniques, and O'Driscoll hopes to increase this yield, something that would help treat more patients.
Her team is also looking at the progenitor cells that produce the beta cells. These stem cells exist inside the pancreas and "differentiate" to become beta cells. How this happens remains unclear in humans but she has already had some success differentiating mouse stem cells that have gone on to produce insulin.
Cold storage of islets or "cryopreservation" is also under study at the NICB. Islets for transplantation must be used quickly because existing storage methods are inadequate, O'Driscoll says, something she hopes to correct.
Islet transplantation is the way to go to eliminate the need for insulin injections, she believes. Whole pancreas transplants require close tissue matching to prevent rejection. "The islet transplants don't require tissue typing, only a blood group match." Islet transplants also only require minor surgery under a local anaesthetic while whole organ transplants represent major surgery.
"The islets are injected into a vein and lodge in the liver where they produce insulin," she explains. The procedure is very new so only short-term results are available but two-year results on 300 patients treated at the University of Miami show that 71 per cent of them remain insulin independent after islet transplantation.
Of the remainder, they are finding that the beta cells continue to produce a background level of insulin that can be supplemented by injection. "That low level of insulin is important to control our blood glucose levels," says O'Driscoll, as it helps to even out glucose highs and lows if the patient response to injected insulin is erratic.
The institute, headed by director Prof Martin Clynes, last month announced a €34-million investment programme, including a new purpose-built €10.4-million research centre. Due for completion in 2005, the centre will help the NICB to greatly broaden the scale of its research activities.