Insulin producing cells have been transferred from one species of rodent to another without rejection, breaking down some of the barriers along the way to a cross-species therapy for humans with Type-1 Diabetes.
Xunrong Lou and Stephen Miller co-authored the study and reported in the journal Diabetes that they successfully transplanted rat islets into mice, allowing the mice to produce insulin from the foreign islets for an extended period of time without dependency on immunosuppressive drugs.
Islets are the powerhouse of the pancreas, overseeing the production of insulin which is used to regulate blood-glucose levels in the body. Diabetics have difficulty producing insulin and researchers have been trying to find ways in which to substitute the faulty islets in humans with foreign replacements. The main problem with this has been the human body’s rigorous immune system, which can easily detect unknown entities (such as animal islets) and perceive them as hostile, causing rejection.
“This is the first time that an interspecies transplant of islet cells has been achieved for an indefinite period of time without the use of immunosuppressive drugs,” said Miller. The mice were able to depend upon the rat islets to produce insulin for at least 300 days before observations finished. Miller commented that this achievement is “a big step forward” in developing a treatment for human diabetes. Pig islets are the prime candidates for alternate controls of human blood sugars. Finding a way to implement pig islets in humans using the same method shown by Lou and Miller in the mice will prove challenging because our own immune systems are far more complex than rodent species.
In the study, a type of white blood cell found in rats was completely removed from the creature’s spleen. The white blood cells were then chemically damaged and injected into the mice. Their damaged state caused the mice T-cells to accept the new entities and not attack them.
The next challenge involved neutralising the mice B-cells which are the main producer of antibodies. Lou found that an injection of B-cell reducing antibodies into the mice eliminated this threat. This is a method already used in human-to-human transplants. The key to not creating an immune response was to carry out these steps simultaneously, so when the mice B-cells naturally returned, they no longer recognised any threat.
Human donors of islets are at an all time low, meaning that Type-1 Diabetes patients are suffering multiple organ damage because they are unable to receive treatment. Having access to islets from other species will allow for their mass production, abolishing islet- transplant waiting lists for diabetics around the world.