Diabetes means increase in blood glucose or blood sugar levels. Insulin is a hormone that is important for metabolism and utilization of energy from the ingested nutrients - especially glucose. Without insulin, too much glucose stays in blood.
Insulin is synthesized in significant quantities only in beta cells of islets of Langerhan in the pancreas. It is secreted primarily in response to elevated blood concentrations of glucose. Insulin thus can regulate blood glucose and the body senses and responds to rise in blood glucose by secreting insulin. In type 1 diabetes, pancreas does not make or make in less quantity insulin.
Treatment of diabetes is a lifelong commitment to: Taking insulin, exercising regularly and maintaining a healthy weight, eating healthy foods nad monitoring blood sugar level. For people with hard-to-control type 1 diabetes, a transplant of insulin-producing islets from a deceased donor is one important way to control their chronic disease, in which their bodies do not produce insulin. However, there is a severe shortage of islet cells from deceased donors. Many patients on waiting lists don't receive the transplant or suffer damage to their heart, nerves, eyes and kidneys while they wait.
Scientists have been trying to transplant cells that produce insulin from other species to humans, but concerns about controlling rejection of transplants from a different species have made that approach insurmountable until now. Scientists from Northwestern Medicine® have successfully transplanted islets, from one species to another. And the islets survived without immunosuppressive drugs.
Scientists persuaded the immune systems of mice to recognize rat islets as their own and not reject them. Notably, the method did not require the long-term use of drugs to suppress the immune system, which have serious side effects. The islets lived and produced insulin in the mice for at least 300 days, which is as long as scientists followed the mice.
In their study they, removed the rat splenocytes (a type of white blood cell located in the spleen) and treated with a chemical that caused their deaths. Next, the dead splenocytes were injected into the mice. The cells entered the spleen and liver and were mopped up by scavenger cells. The scavengers processed the splenocytes and presented fragments of them on their cell surface, triggering a reaction that told the T cells to accept the subsequently transplanted rat islets and not attack them.
But rejection was still a threat. A unique challenge of an interspecies transplant is controlling the B cells, immune cells that are major producers of antibodies. Initially, when scientists transplanted the rat islets into the mice, the mouse immune system started producing antibodies against the rat cells causing rejection.
To solve the problem, scientist realized that they needed to kill off the B-cells at the same time they injected the donor islets into the mice. Thus, they gave the mice B-cell depleting antibodies -- already used in a clinical setting in human transplants. When the B-cells naturally returned after the transplant, they no longer attacked the rat islets.
Their ultimate goal is to be able to transplant pig islets into humans, but the barrier from rats to mice is probably lower than from pigs to humans. Now they are trying to figure out why the B-cells are different when they come back.
The study is published in the journal Diabetes.
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