In a First, Diabetic Man Receives Insulin-Producing Cells His Body Won’t Reject—No Needles or Pills

A new treatment for type 1 diabetes is moving closer to reality.

In late 2024, a 46-year-old Swedish man received 17 injections of a unique pancreatic cell cocktail. The cells, donated from a healthy stranger, had been stripped of two critical genes that trigger immune rejection.

For the next three months, the cells evaded the recipient’s immune system and produced insulin, all without the need for immunosuppressive drugs. Results from the trial, the first of its kind, were published this month in The New England Journal of Medicine.

“It’s a major breakthrough, and it’s remarkable,” Bernhard Hering at the University of Minnesota Twin Cities, who wasn’t involved in the study, told Science.

In type 1 diabetes, the body’s immune system attacks and destroys pancreatic cells that pump out insulin, making it difficult to control blood sugar levels. The disease can be managed with carefully timed insulin injections. But it’s a treatment, not a cure.

“Intensive insulin therapy delays the onset and slows the progression of long-term complications,” and it’s been used for more than 100 years, wrote study author Per‑Ola Carlsson and team at Uppsala University, who collaborated with Sana Biotechnology on the study. But people with type 1 diabetes still have a higher risk of serious heart and blood-vessel problems and a shortened lifespan.

A cure would replace damaged cells with healthy ones. Insulin-producing cells clump together with other pancreatic cells into rounded blobs called islets. These can be isolated and transplanted into people with diabetes—often multiple at a time—as a sort of back-up generator to produce insulin. But the recipient has to take immunosuppressive drugs for life, which dampens their ability to fight off infections and increases the risk of cancer. Cells that evade the immune system could, in theory, provide long-term care and better quality of life.

An Immune Puzzle

The immune system is a cellular brigade, effective at fighting off infectious diseases. But it can also become an adversary in transplantation.

Each cell has a unique protein fingerprint on its surface. The immune system recognizes these as either friend—part of the body—or foe. Islet cells from a stranger immediately activate a swarm of immune attacks.

Killer T cells, true to their name, release proteins that tear the transplanted cells apart. B cells churn out a slurry of antibodies that grab onto the transplants and activate a cascade of immune proteins to recruit other cell types, such as macrophages—giant blobs that literally eat up any tagged enemy—and natural killer cells. The latter are immune-system assassins, capable of killing cells that lack normal proteins that would usually mark them as friendly.

The entire immune brigade activates after a transplant and this leads to rejection. Without immunosuppressive drugs, donated islets can’t survive in people with diabetes.

A Solution in the Genes

A few years back, the authors of the new study found a way to strip immune-triggering proteins from donated islet cells.

They zeroed in on two major proteins, HLA-I and HLA-II, that dot the cells’ surfaces. Using the gene-editing system, CRISPR, they snipped out genes encoding both proteins. Theoretically, this would protect the cells from immune rejection.

But the strategy is a double-edged sword. The proteins are normal parts of a cell. Getting rid of them causes the immune system to view the engineered cells suspiciously and target them with natural killer cells. So, the team added another protein called CD47. This protein acted like camouflage shielding the cells from the immune brigade.

Tests in diabetic models of mice and a monkey found both incorporated the cells without needing immunosuppressants. Results from the monkey were especially promising. The engrafted cells pumped out enough insulin to sustain the animal’s blood sugar levels for at least six months without the need for additional insulin and no observed side effects.

Encouraged by the results, the team started a clinical trial. They took islets from a 60-year-old donor with the same blood type as the trial recipient and edited them. Not all cells retained the changes. Although nearly all were stripped of immune-triggering HLA proteins, less than half contained the added immune-soothing CD47 protein.

The final product was an amalgamation of cells, each with a different genetic profile.  As a safety measure, the team injected a relatively small dose—80 million engineered cells—into the participant’s arm while he was under general anesthesia. He tolerated the therapy well and was released from the hospital the next day.

Over the next three months the team monitored his immune system. Unedited cells provoked a strong but transient T-cell attack, which declined after a week. Meanwhile, cells stripped of both HLAs still caught fire from macrophages—the “cell-eaters”—and natural killer cells.

Cells that had been fully edited, however, escaped the immune onslaught entirely and continued producing insulin for three months. In lab tests, the team “did not detect any immune response targeting” the cells, they wrote.

Slow and Steady

The volunteer was diagnosed with type 1 diabetes at five years of age. Before the trial, his islets struggled to produce insulin, and he showed signs of an over-zealous immune system.

Following treatment with the engineered cells, however, his insulin levels increased after slurping a smoothy full of fats, protein, and carbohydrates. A follow-up imaging test found the transplanted cells thriving in his forearm muscle. Twelve weeks after injection, the man’s arm had functional islets that could produce insulin—without taking any immune-suppressing drugs.

He experienced some mild side effects, including blood clots in small, surface veins at the site of injections. These can be treated with heat or blood-thinners.

“To my mind this is a huge success,” Carlsson told Science.

The study moves us closer to a cure for diabetes. Compared to the animal studies, the man only received a very small dose (roughly seven percent of the amount used in animals). But his insulin response tracked with predicted outcomes based on previous studies. Upping the number of engineered cells could nix the need for insulin injections.

Other cell therapy efforts for type 1 diabetes are underway. Vertex Pharmaceuticals recently published promising results of a stem-cell-based therapy. The treatment slashed dangerous blood sugar spikes and dips in type 1 diabetic volunteers over the course of a year and without the need for insulin. However, all of them had to take immunosuppressant drugs.

Immune-evading cells have “long been viewed as a holy grail,” wrote the authors.

The team is now exploring ways to engineer insulin-producing cells from stem cells to increase production. They’re also keeping up with the recipient to make sure the transplanted cells continue making insulin and evading immune attacks.