Scientists have successfully treated mice with type 1 diabetes by creating a 'mixed immune system' combining donor and patient components.
JCI - Curing autoimmune diabetes in mice with islet and hematopoietic cell transplantation after CD117 antibody-based conditioning
https://www.jci.org/articles/view/190034
Scientists cured type 1 diabetes in mice by creating a blended immune system | Live Science
https://www.livescience.com/health/scientists-cured-type-1-diabetes-in-mice-by-creating-a-blended-immune-system
Patients with type 1 diabetes need to take insulin for life to control their blood sugar levels. However, even with the best treatment, they are at high risk of complications such as heart disease, kidney disease, and eye problems.
Therefore, in recent years, a treatment method called islet transplantation has been attempted, which involves transplanting islets, a group of cells that contain insulin-producing cells. In islet transplantation, only the islets are isolated from the pancreas of a donor who has suffered cardiac arrest or brain death, and transplanted into a patient with type 1 diabetes via intravenous infusion.
However, if left untreated, the transplanted islet cells would be attacked by the patient's immune system, requiring the patient to take strong immunosuppressants for life to prevent rejection. For this reason, islet transplantation has been performed only on patients with severe type 1 diabetes who require transplants of other organs.
One way to avoid immune system problems associated with islet transplantation is to 'transplant hematopoietic stem cells that produce white blood cells simultaneously, thereby creating a system in the patient's body that produces white blood cells that do not attack the islets.' By transplanting hematopoietic stem cells derived from the same donor as the islets, it may be possible to create a 'mixed immune system' that does not recognize the transplanted islets as foreign and does not have cells that attack the islets.
This process requires removing stem cells from the patient's own bone marrow. This necessitates completely destroying the patient's immune system through chemotherapy and radiation therapy, leaving the patient at high risk of infection for several weeks. 'It's like a game of musical chairs. You can't transplant donor cells unless you remove the recipient stem cells from their seats,' says Judith Sizzle , professor at Stanford University School of Medicine and co-author of the paper.
Sizzle and his research team hypothesized that there might be a less toxic method to 're-educate' the patient's immune system rather than erasing it. Sizzle explains, 'When donors and patients are mixed, the donor's immune system can influence the behavior of the patient's immune cells.'
In this study, the research team devised a multi-step process using multiple antibodies, low-dose radiation, and
The experimental results showed that these immune system modulation processes created space in the patient's bone marrow for donor-derived stem cells. It was also confirmed that various parts of the immune system were suppressed for a sufficient period of time for the donor-derived stem cells to take root, without killing off all of the patient's own stem cells.
In this way, the transplanted stem cells from the donor gradually matured, and in the process, they trained the patient's entire immune system to accept the donor-derived pancreatic islets. Furthermore, it has been reported that the matured donor-derived stem cells eliminated the patient's cells, which were trained to specifically attack the pancreatic islets, thus eliminating the cause of the autoimmune disease that leads to type 1 diabetes.
The treatment took about 12 days from start to finish, but during that time, the patient's immune system was not completely destroyed, and the amount of radiation used was less than that used in a typical bone marrow transplant. 'We made this treatment much milder,' Sizzle said.
Mice that received transplanted donor stem cells and pancreatic islets continued to produce insulin 20 weeks after treatment. Blood tests and post-mortem analysis also confirmed that their immune systems were functioning normally and that they did not reject the transplanted pancreatic islets.
Many challenges remain before this treatment can be applied to humans. For example, some of the antibodies used to treat mice do not have similar drugs approved for humans, and there is a shortage of pancreatic islet transplant donors. Furthermore, creating a mixed immune system between the donor and the patient requires a delicate balance, which is another hurdle to applying the treatment to humans.
Regarding these research findings, Professor John DiPercio, head of the cell therapy division at the University of Washington, pointed out that because humans have a significantly longer lifespan than mice, which live for only one to two years, it is difficult to maintain a mixed immune system in the human body for extended periods. He added, 'This is a way to potentially cure type 1 diabetes. Theoretically, this is certainly a big step forward.'
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