Worth Reading: Stanford Cures Type-1 Diabetes in Mice Without Insulin or Immune Suppression | Good News Today

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Quick summary: This story highlights recent developments related to diabetes, showing how constructive action can lead to meaningful results.

In an experiment that exceeded scientists’ expectations, mice had their type-1 diabetes cured through a double-transplant method.

Additionally, there was no host rejection of one one of the two types of transplanted cells, and the immune system didn’t attack the other, resulting in a diabetes cure without any side-effects.

Obviously caveats must be drawn from a mouse model such as this, but the results have supercharged the team’s determination to try and see if they can replicate the success in humans.

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“The possibility of translating these findings into humans is very exciting,” said Seung Kim, MD, PhD, and multidisciplinary professor at Stanford University.

“The key steps in our study—which result in animals with a hybrid immune system containing cells from both the donor and the recipient—are already being used in the clinic for other conditions. We believe this approach will be transformative for people with type 1 diabetes or other autoimmune diseases, as well as for those who need solid organ transplants.”

Unlike onset, or type-2 diabetes, type-1 is an autoimmune disorder that manifests in the patient’s immune system attacking their own islet cells, located in the pancreas and responsible for producing the hormone insulin, which helps control blood-glucose levels.

This new study from Stanford Medicine saw type-1 diabetic mice receive a transplant of islet cells and blood stem cell from a healthy mouse.

This combination proved to be virtually magical, and for 6 months, the treated mice needed no insulin injection, nor medication to suppress graft-versus-host disease, an immune-system response to transplantation that can be debilitating.

Stanford University described the results of the trial as particularly exciting because the pancreatic islet cells from the healthy donor have “two targets on their backs.” The first is that they’re transplanted cells from a different organism, and the second is that they are the type of cell that the autoimmune disorder spontaneously destroys.

“Just like in human type 1 diabetes, the diabetes that occurs in these mice results from an immune system that spontaneously attacks the insulin-producing beta cells in pancreatic islets,” Kim said. “We need to not only replace the islets that have been lost but also reset the recipient’s immune system to prevent ongoing islet cell destruction. Creating a hybrid immune system accomplishes both goals.”

Using a pre-transplant preparatory drug, used in a previous study of the same kind published by the team in 2022, the mixture of transplanted islet cells and hematopoietic stem cells created an immune system of mixed origin that suddenly snapped back into good working order and prevented type-1 diabetes in 19 out of 19 mice, while another 9 out of 9 mice who had suffered from long-term type-1 diabetes had their disease cured.

For the full six-month follow-up, none of the 9 needed an insulin injection or immuno-suppressant drugs to stop their immune system attacking the transplanted islet cells.

As a side-discovery of the experiment, Dr. Judith Shizuru, a member of the study team, had been working to devise a gentler and more benign, pre-treatment approach to blood stem cell transplantation. This procedure has been used to seemingly cure some cancers, including leukemia and lymphoma, but it requires intense, sometimes life-threatening radiation therapy to wipe out the immune cell population in the patient’s bone marrow.

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This allows the time and space for the properly-functioning donated stem cells to take hold, and is being hypothesized as a potential treatment for autoimmune diseases like rheumatoid arthritis and lupus.

Dr. Shizuru applied a method to the mice that was far less vigorous, “knocking back” the bone marrow just enough, which was shown to be successful.

In regards to those other currently-incurable autoimmune diseases, the research holds much promise, but for type-1 diabetes, two factors mean the mouse model doesn’t immediately translate to humans.

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The first is that pancreatic islet cells can only be obtained from a deceased donor, while the blood stem cell transplant must come from the same person. Because of the size difference between the animals, it’s unclear how many millions of islet cells would be needed to see the same effect in humans.

Future work will include discovering a way of cultivating pancreatic islet cells in a lab through pluripotent stem cells, or perhaps finding a way to increase their survivability.

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