On a Sunday morning in May 2025, a multidisciplinary Stanford Medicine team gathered around a milestone years in the making. Some clinicians and scientists were in the hospital room. Others followed along by text, staying closely updated despite the weekend timing. For Marina Basina, MD, an adult endocrinologist at Stanford Department of Medicine, the moment carried the weight of a decade-long effort for her and the whole Stanford pancreatic Islet Transplantation and immune tolerance initiative (SPIRIT) team: the hope of moving closer to a true cure for type 1 diabetes.

The procedure was an islet cell transplant, in which insulin-producing cells from a donor pancreas are infused into a patient’s liver. This transplant also included an immune tolerance protocol, an experimental approach designed to help the body better accept donor cells.The protocol represents an important step toward a future goal: reducing or potentially eliminating the need for lifelong immunosuppression after islet transplantation.

For patients with the most dangerous complications of type 1 diabetes, including those who can no longer sense when their blood sugar is falling, that possibility could be life-changing. Here, Basina discusses Stanford’s SPIRIT program, why type 1 diabetes remains so difficult to manage, and what this first case may mean for the future of islet cell transplantation.

For readers who may not be familiar, why is type 1 diabetes so challenging for some patients to manage?

Even as continuous glucose monitoring, or CGM, and automated insulin delivery systems, often called hybrid closed-loop systems, have become standard of care for many people with type 1 diabetes, substantial management challenges remain.

Diabetes management is still exhausting. Patients have to count carbohydrates, tell their insulin pump when they are eating, and make insulin adjustments during exercise, illness, stress, and many other situations that current automated insulin delivery algorithms cannot fully predict.

Insulin pharmacology is another limiting factor. By that, I mean the way insulin behaves in the body: how quickly it starts working, when it reaches its strongest effect, and how long it lasts. Even rapid-acting insulin works significantly more slowly than the insulin produced naturally by the body. In someone without diabetes, insulin is released almost immediately and very precisely in response to changes in blood sugar. Injected or pumped insulin cannot fully match that timing.

There is also the risk and fear of hypoglycemia, or low blood sugar. Low blood sugar can cause shakiness, sweating, confusion, weakness, and, in severe cases, seizures or loss of consciousness. Patients also deal with device burden, alarm fatigue, sleep disruption, skin irritation from device adhesives, and fear of long-term diabetes complications. All of this contributes to significant psychological burden and diabetes distress.

According to a study published in Diabetic Medicine, people with type 1 diabetes make an average of 180 decisions each day related to their diabetes.

Some patients with severe type 1 diabetes may undergo a full pancreas transplant, which is a major surgical procedure. How does an islet cell transplant differ from a traditional pancreas transplant, and why might this newer approach be beneficial for patients?

In islet cell transplantation, insulin-producing cells are isolated from a donor pancreas and infused through a catheter into the liver through the portal vein, a major blood vessel that carries blood to the liver. The islet cells can then begin producing insulin inside the liver.

This is a significantly less invasive procedure than whole pancreas transplantation, which requires major abdominal surgery. The surgical risks are relatively low with islet cell transplantation, and the recovery period is shorter than with a full organ transplant.

Many recipients regain awareness of low blood sugars, experience more stable glucose levels with fewer sharp highs and lows, and have less diabetes-related burden. Some achieve insulin independence, meaning they no longer need insulin injections or pump therapy, while others still need insulin but at lower doses and with better glucose control.

Stanford recently performed what has been described as the first allogeneic islet cell transplant with tolerance induction. What made this procedure such an important milestone?

The first allogeneic islet cell transplant with tolerance induction was performed in May 2025. “Allogeneic” means the transplanted cells came from another person, rather than from the patient’s own body. “Tolerance induction” refers to an approach designed to train the immune system to accept those donor cells instead of attacking them.

It was an important milestone because it was the result of 10 years of work by a multidisciplinary team, in collaboration with UCSF and advisors from other institutions. It was also the first islet cell transplant ever performed using this protocol.

One of the most exciting aspects of this work is the potential to reduce the need for lifelong immunosuppressive medications. Why is that such a significant advancement for patients?

Reducing or eliminating the need for lifelong immunosuppressive medications would be a major advance for people receiving islet cell transplants. These medications are currently necessary to prevent rejection, which happens when the immune system recognizes transplanted cells or organs as foreign and attacks them. But immunosuppressive medications can cause significant long-term complications.

These medications can also be toxic to the islet cells themselves, increasing the risk that the new islets will fail. They can have a diabetogenic effect, meaning they can worsen blood sugar control or contribute to diabetes, and they also increase the risk of infection, cancer, and kidney damage.

Tolerance induction aims to “teach” the immune system to accept the transplanted islets as its own tissue. By introducing donor blood stem cells alongside the beta cell transplant — beta cells are the insulin-producing cells within the islets — the recipient’s immune system is re-educated to recognize the donor cells as self rather than foreign. The goal is for the patient’s body to accept the transplanted cells without ongoing immunosuppressive therapy.

Tolerance induction through mixed chimerism offers the possibility of a true cure. Mixed chimerism means that immune cells from both the donor and the recipient exist together in the patient’s body, helping the immune system tolerate the transplant. This represents one of the most important potential advances in transplant medicine.

The patient who received the transplant reportedly experienced dramatic improvements in blood sugar control after the procedure. From a clinical perspective, what does that kind of improvement mean for quality of life?

In addition to remarkable improvement in blood sugar control, with time in range of continuous glucose monitoring greater than 90%, and an insulin dose reduction of about 80%, the patient experienced a significant improvement in quality of life.

“Time in range” refers to the percentage of time a person’s blood sugar stays within a healthy target range. For someone with type 1 diabetes, spending more time in range usually means fewer dangerous lows, fewer high blood sugar episodes, and less day-to-day worry about glucose swings.

According to the patient, they were able to return to work full time. They started running again, something they had not been able to do in the past decade. They gained much more energy and had a reduced burden from needing to administer insulin boluses, which is an extra dose of insulin given around meals or snacks to manage the rise in blood sugar after eating.

The SPIRIT team is currently focusing on patients with hypoglycemia unawareness. Can you explain what that condition is and why these patients may particularly benefit from this approach?

Hypoglycemia unawareness is currently the primary indication for pancreatic islet cell transplantation in adults with type 1 diabetes.

Normally, when blood sugar drops too low, the body gives warning signs, such as shakiness, sweating, a racing heart, hunger, or anxiety. These symptoms alert a person to eat or drink something with sugar before the situation becomes dangerous.

In long-standing type 1 diabetes, some patients lose the ability to sense falling blood glucose levels. This is called impaired awareness of hypoglycemia, or hypoglycemia unawareness. It can lead to recurrent low blood sugar events and severe episodes involving seizures or loss of consciousness. These episodes can be life-threatening and profoundly disabling.

It also makes it much harder to achieve target blood sugar levels because of the fear of low blood sugars. Patients frequently reduce or stop exercising because of the increased risk of hypoglycemia during physical activity.

Were there any moments during your work with SPIRIT that felt especially meaningful or memorable to you personally?

One of the most memorable moments was the day of the transplant. It felt like such an important multidisciplinary effort, with the most important goal of finding a cure for type 1 diabetes.

I also remember the exciting moment of the mixed meal tolerance test, which was done six months after the transplant. A mixed meal tolerance test is a way to measure whether the body can produce insulin in response to food. For this test, our patient had been off insulin for nine hours. The patient then received a Boost shake, and we checked several blood markers at baseline and at multiple time points after the shake.

As the results came back, it was amazing to see that C-peptide levels were coming back in the normal range. C-peptide is a marker that shows whether the body is producing its own insulin. Before islet cell transplantation, that level had been undetectable. This was a measure of the success of the procedure.

Looking ahead, what are the next steps for the SPIRIT program, and what are you most hopeful about moving forward?

The next step is to perform the procedure in two to three more patients and expand the preliminary data obtained from our first patient case. This will require seeking funding opportunities.

Longer term, the goal is to achieve sustained chimerism or immune tolerance, meaning that the immune system is permanently re-educated to accept donor cells as self. In the current state, mixed chimerism is temporary in many patients. Donor cells gradually disappear, and the patient’s own cells take over, which can lead the immune system to begin attacking the transplanted cells.

When the next generation of islet cell products becomes available, including potentially lab-grown insulin-producing cells in the future, permanent immune tolerance protocols will become critically important. Together, these advances could allow islet replacement therapies to help many more people with type 1 diabetes in the years ahead.

I would also like to highlight the Autologous Islet Transplantation component of the SPIRIT program. Autologous islet transplantation is an FDA-approved procedure performed to preserve insulin production and reduce the risk of diabetes in patients undergoing total pancreatectomy for debilitating chronic pancreatitis. The program is led by Dr. Walter Park, Medical Director of the Pancreas Clinic at Stanford, in collaboration with hepatobiliary surgeons Dr. Varvara Kirchner and Dr. Brendan Visser, and me as the endocrinologist overseeing diabetes management. To date, nine autologous islet transplantation procedures have been successfully performed at Stanford.