Doctors in St. Louis have succeeded in transplanting insulin-producing cells from rats to mice, raising the possibility that cross-species transplant may eventually be used to help human diabetics.
The rat-to-mouse transplants, accomplished this spring by a team at Washington University, have not only returned diabetic mice to normal, they have also caused many of the serious side effects of the disease -- eye, blood vessel and kidney problems -- to disappear.
"Our next step is to transplant the insulin-producing cells of pigs into mice," said Dr. Paul E. Lacy, who, with Drs. Joseph M. Davie and Edward H. Finke, performed the transplants from rats. "If that works, there is a distinct possibility that the same transplant will work in humans."
Diabetes occurs when the pancreas fails to produce enough insulin, a hormone, to control the level of sugar in the blood. An estimated 300,000 Americans must take daily injections of insulin to survive.
But while the injections control the disease, they cause large swings in blood sugar. And diabetes is often accompanied by other problems: internal bleeding in the eye, which can cause blindness, and damage to blood vessels elsewhere in the body which can lead to heart attack, stroke, loss of limbs and kidney failure.
No practical way has been found either to collect human insulin or to transplant human cells, which is why doctors have turned to animals.
The breakthrough in the experiments at Washington University is the successful transplant of rat insulin cells into diabetic mice, proving that such transplants can cross species barriers. Insulin cells had been transplanted from one identical rat to another and from a white rat to a black rat but never from a rat to a mouse.
The problem has long been rejection. The recipient's immune system would treat the transplant as foreign material and destroy it.
Lacy, Davie and Finke isolated tiny clusters of pancreas cells that produce insulin -- known as Islets of Langerhans -- maintained them in a healthy state at room temperature and then injected them into 10 diabetic mice along with a single injection of a drug, such as cortisone, that suppresses the immune system.
Keeping the rat islets at room temperature for seven days changed or destroyed the white blood cells that triggered rejection of the transplant by the mice. This allowed a single injection of an immune-suppressive drug instead of multiple injections, which can be toxic or even lethel to the recipient.
Three of the 10 diabetic mice given the rat insulin cells rejected the transplants in anywhere from 32 to 51 days but the other seven reached normal blood sugar levels in as few as two days and have maintained that level for the last 116 days.
"We will follow their progress right out to 200 days," Lacy said, "and then concentrate our attention on isolating and transplanting pig insulin-producing cells into mice."
Doctors stressed that the treatment of human diabetics with transplanted animal insulin cells is not imminent. Isolating the insulin cells of pigs and cattle, the two animals whose pancreases and insulin are similar to humans', has not been done.
The next step at Washington University School of Medicine is to work out an experiment in which insulin-producing cells can be removed from a pig's pancreas and kept alive. One reason that is not a simple experiment is that the insulin-producing cells comprise only 2 percent of any animal's pancreas.
Another question is whether transplanted cells from animals to humans would be metabolically normal for long periods of time. Further research is also needed to identify the best site and minimum number of transplanted cells to regulate blood sugar levels before transplants can be tried in humans. c