Stanford researchers cure type 1 diabetes in mice by resetting the body’s immune system

A team at Stanford Medicine has delivered something people with Type 1 diabetes have waited decades to hear: a cure in animals that does not rely on toxic chemotherapy or lifelong immune drugs. In carefully designed mouse studies, scientists rebuilt the immune system and replaced lost insulin cells. Blood sugar returned to normal. Insulin shots stopped. The disease did not return.

Type 1 diabetes begins when your immune system turns against you. It targets pancreatic islet cells that make insulin, the hormone that controls blood sugar. Once those cells are gone, daily injections replace a job your body once did on its own.

Doctors have tried islet transplants. Some worked for a while. Most did not. The immune system often attacked the new cells. Patients also needed drugs for life to prevent rejection, which raised the risk of infections and cancer.

Stanford’s idea went deeper. Instead of only replacing the cells that make insulin, researchers repaired the immune system that destroyed them.

Bone marrow transplants can replace a faulty immune system. Yet the usual process uses harsh radiation or chemotherapy to wipe out the old marrow. That can be dangerous and painful.

The Stanford team chose another route. They used a targeted antibody that clears space in the bone marrow without wiping it out. They paired it with low-dose radiation, brief immune-reducing drugs and baricitinib, a medication already used for autoimmune diseases.

This “non-myeloablative” approach creates room for donor cells without wrecking the marrow.

Researchers then transplanted blood-forming stem cells from donors into mice bred to develop Type 1 diabetes. These animals closely mimic the human disease. Some also received healthy pancreatic islets from the same donors.

What followed surprised even the scientists.

Every mouse that developed a hybrid immune system was cured. Blood sugar normalized. Insulin stopped. Health held steady for months.

When researchers later removed the kidney that held the transplanted islets, diabetes returned. That proved the new cells did the work.

“The possibility of translating these findings into humans is very exciting,” said Seung K. Kim, MD, PhD, senior author of the study. “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.”

The work appeared Nov. 18 in the Journal of Clinical Investigation. Preksha Bhagchandani, a graduate and medical student, led the research.

This new immune state is called mixed chimerism. Your body carries both donor and personal immune cells. The two systems live side by side instead of battling.

In the Stanford experiments, about three-quarters of immune cells came from donors. Yet the defenses still worked. When researchers tried to add islets from a third, unrelated donor, the body rejected them. That showed immunity stayed sharp.

No mouse developed graft-versus-host disease, a feared problem where donor cells attack healthy tissue. Weight gain stayed normal. Blood counts looked healthy.

The cure also worked in animals with severe disease. Of nine mice with long-standing diabetes, all nine were restored to normal blood sugar after treatment.

The team also tested young mice on the road to diabetes. Untreated, most develop the disease. After treatment, none did.

Their pancreas showed little immune damage. In untreated mice, immune cells often swarm the islets. In treated animals, the tissue looked intact.

This approach did more than fix disease. It blocked it.

How did the attack stop? By erasing the cells that start it.

Researchers tracked aggressive T cells that hunt insulin-making cells. In treated mice, those attackers nearly vanished.

To be sure, scientists transferred immune cells from cured mice into animals without immunity. If danger lingered, diabetes would appear. It did not.

Cells from untreated diabetic mice, in contrast, triggered disease in every recipient.

Inside the thymus, the immune training ground, donor cells took root. New immune cells learned what should count as “self.” Harmful cells were deleted. Protective ones grew.

The immune system was not silenced. It was corrected.

This was an animal study. Yet key parts already exist in human medicine.

The antibody used in mice has a human cousin, briquilimab, now tested in blood disorders. Baricitinib is FDA-approved. Low-dose radiation is common in transplant care.

Judith Shizuru, MD, PhD, who helped pioneer gentler transplant methods, emphasized safety. “The challenge has been to devise a more benign pre-treatment process, diminishing risk to the point that patients suffering from an autoimmune deficiency that may not be immediately life-threatening would feel comfortable undergoing the treatment,” she said.

The new study builds on years of work at Stanford. The late Samuel Strober, MD, PhD, once showed that hybrid immunity could allow long-term organ acceptance without rejection drugs. Some kidney recipients kept donated organs for decades.

Islets usually come from deceased donors and must match the blood cell donor. Supply is limited. One donor may not yield enough cells for an adult.

The team is exploring lab-grown islets from stem cells. They are also testing ways to boost cell survival and insulin output.

The goal reaches beyond diabetes. The same strategy may help lupus, rheumatoid arthritis and even mismatched organ transplants.

Kim sees a door opening. “The ability to reset the immune system safely to permit durable organ replacement could rapidly lead to great medical advances,” he said.

For families touched by Type 1 diabetes, the word “cure” has felt out of reach. This work makes it sound closer.

Research findings are available online in the Journal of Clinical Investigation.

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