Experts at Stanford Medicine have taken a promising step forward in developing a potential cure for Type 1 diabetes. This new transplant approach can eliminate or reduce the need for lifelong medications to suppress the immune system.

The achievement was the work of the aptly named SPIRIT, or Stanford Pancreatic Islet Replacement and Immune Tolerance, Program. The program brings together specialists from across Stanford Medicine, including:

• Stephan Busque, MD, MSc, transplant surgeon and surgical director of the Adult Kidney, Islet, and Pancreas Transplant Program
• Jane Tan, MD, PhD, transplant nephrologist and medical director of the Adult Kidney, Islet, and Pancreas Transplant Program
• Everett Meyer, MD, PhD, blood and marrow transplant specialist and director of the Cellular Immune Tolerance Program
• Marina Basina, MD, endocrinologist
• Avnesh Thakor, MD, PhD, interventional radiologist

“In May 2025, we successfully performed the first ever allogeneic islet cell transplant with tolerance induction,” says Dr. Busque. “The protocol combines established methods for transplanting pancreatic islet cells with Stanford Medicine’s extensive experience in reducing post-transplant immune response. While there’s more work ahead, we feel we’re at the start of a promising new era.”

Standing on the shoulders of pioneers

Breakthroughs in transplant medicine often happen in great leaps. Allogeneic islet cell transplant started when researchers realized they didn’t need to transplant the whole pancreas.

The pancreas produces both digestive enzymes and hormones. The hormone-producing cells, called islet cells, can be isolated from the healthy pancreas of a deceased donor. They can then be placed into a vein in the liver using a minimally invasive procedure. Once transplanted, the islet cells survive and produce insulin.

Innovations in immunosuppressive therapy helped make allogeneic islet cell transplant possible. But the long-term use of these drugs is rife with complications. Results from a phase 3 trial of allogeneic islet cell transplantation highlighted the need for transplant protocols that don’t require such intensive immunosuppressive therapy¹. That’s where Dr. Busque and the SPIRIT team came in.

Stanford Medicine has been a world leader in transplant tolerance for decades, starting with professor of immunology and rheumatology, Sam Strober, MD. Dr. Strober was a visionary who spent his career developing ways to reduce the need for immunosuppressant drugs following solid organ transplant. Dr. Busque and other researchers transformed this work into clinical practice, including its application to allogeneic islet cell transplantation.

Strategies to induce transplant tolerance

Inducing tolerance in patients undergoing islet cell transplantation is complex. Two of the main methods include:

• Mixed chimerism: This approach uses a bone marrow infusion from the islet cell donor to establish a mixed immune system in the patient. With mixed chimerism, the patient’s immune system doesn’t see the transplanted islet cells as foreign and, therefore, doesn’t attack them.
• Regulatory T cells: This approach harnesses regulatory T cells whose role is to prevent the body from attacking its own cells. T cells can be engineered in a lab and given to a patient to help protect the transplanted islet cells.

“Our investigational protocol allows us to use either method with allogeneic islet cell transplantation,” says Dr. Meyer.

Making history in allogeneic islet cell transplantation

For this first patient, the SPIRIT team worked with UCSF transplant specialists, Greg Szot, MS, director of clinical islet processing core and Andy Posselt, MD, PhD, pancreas transplant surgeon, to isolate the islet cells from the donor pancreas. The bones from the donor were also available, so the team chose to use the mixed chimerism approach to induce tolerance. The bone marrow infusion was prepared at Stanford Medicine from vertebrae using an extraction process developed by Kent Jensen, PhD, assistant director of the Stanford Diabetes Research Center.

The procedure went smoothly. The patient received the islet cells on one day and the bone marrow cells the day after. Their total hospital stay was four days. Compared with a pancreas transplant, which takes weeks to months to recover, the procedure was very well tolerated. In the future, it could likely be an outpatient procedure.

After surgery, an increase in C-peptide levels indicated that the transplanted islet cells had successfully grafted inside the liver and were producing insulin. “The patient also showed significant improvement in blood sugar control,” says Dr. Basina. “The percentage of time spent in the target blood sugar range increased from less than 40% before surgery to near 100%.”

Because the patient previously had a kidney transplant, the team could not assess the outcomes related to immunosuppressive therapy. They aim to do this in future patients.

Where does SPIRIT go next?

Buoyed by the promising results of their first case, the SPIRIT team is excited to offer the new treatment to other candidates. For now, they are focusing on people with hypoglycemia unawareness, which affects about one in four people with Type 1 diabetes. Hypoglycemia unawareness is a life-threatening condition in which people don’t experience symptoms when their blood sugar drops.

The SPIRIT team’s ability to continue this project depends on securing additional funding. They’re exploring all options and have launched a fundraising campaign. Start-up support will allow the team to firmly establish the merits of the procedure so they can apply for larger grants.

“Our track record is exceptional,” says Dr. Busque. “In kidney transplantation, we’ve had remarkable success in eliminating the need for immunosuppressive therapy with closely matched donors. We expect this new protocol for allogeneic islet cell transplantation to yield similar life-changing results for people with Type 1 diabetes.”

¹Hering BJ, et al. Clinical Islet Transplantation Consortium. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia. Diabetes Care. 2016 Jul;39(7):1230-40.

Learn more about Islet Transplant, part of Stanford Health Care’s Transplant Program.