Researchers from Northwestern Medicine managed to transplant islet cells (beta cells) from rats into mice without the need for immunosuppressive medications – and the islet cells survived. The scientists described this as the first step toward animal-to-human transplant of insulin-producing cells. The study was published in the journal Diabetes.
Beta cells are a type of cell in the islets of Langerhans (islets) in the pancreas. Beta cells produce insulin, a hormone that facilitates the transportation of glucose into all the cells in the body – without insulin glucose cannot enter cells, and they perish. Beta cells are also known as islet cells.
The scientists managed to develop a new way of successfully conducting xenotransplantation that prevented rejection of the islets. Xenotransplantation means transplanting an organ, cells or tissue from one species to another. Rejection has been a huge problem in xenotransplantation.
Study co-senior author, Stephen Miller, said:
“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. It’s a big step forward.”
Xunrong Luo, M.D., also co-senior author, said “Our ultimate goal is to be able to transplant pig islets into humans, but we have to take baby steps. Pig islets produce insulin that controls blood sugar in humans.”
For patients with type 1 diabetes who find it hard to control their disease, receiving transplanted islet cells from a deceased donor can help enormously. Islet transplantation even reverses the progression of atherosclerosis. Unfortunately, there is a serious shortage of islet cells from deceased donors. A large number of type 1 diabetes patients suffer serious kidney, heart, eye and nerve damage while they wait for a donor.
If beta cells from other animals, such as pigs could be made available, the shortage would be solved. However, until this breakthrough, experts have believed that xenotransplantation of islet cells was virtually impossible, given the problem with controlling rejection. Using immunosuppressive medications long-term has serious side effects.
In this latest animal experiment, the researchers managed to persuade the immune system of mice to see rat beta cells as their own, and not attack (reject) them. The mice did not need the long-term use of immunosuppressive drugs.
The scientists monitored the mice for 300 days, and during that time the transplanted beta cells continued producing insulin.
Dr. Luo admitted that it is probably easier to get mice to accept tissue from rats than, for example, getting a human to accept islet cells from a pig. He emphasized that this is a “first step” towards interspecies islet transplants without immunosuppressive medications.
Splenocytes are a type of white blood cell located in the spleen. The scientists removed the rats’ splenocytes and treated them with a chemical that killed them. The dead splenocytes were then injected into the mice. They entered the liver and spleen and were “mopped up by scavenger cells”.
The scavenger cells processed the splenocytes and presented their fragments on their cell surface. This primed the T-cells to accept them.
There was still a threat of rejection, the authors explained. A major problem in xenotransplantation is controlling the B cells. B cells are major producers of antibodies. Soon after receiving the rats’ islet cells, the immune systems of the mice started producing antibodies, causing rejection.
The team realized that what they needed to do was kill off the B-cells at the same time the donor islets where injected into the mice. Dr. Luo and team gave the mice B-cell depleting antibodies, something doctors already do in human transplants. When the B-cells naturally came back after the transplant, the rat islet cells were not attacked, i.e. there was no rejection.
Luo said “With this method, 100 percent of the islets survived indefinitely. Now we’re trying to figure out why the B-cells are different when they come back.”