Researchers at Karolinska Institutet in Stockholm have developed an optimized protocol for reliably generating insulin-producing beta cells from human stem cells. In mouse experiments, the transplanted cells fully restored blood glucose regulation. The study, published on April 16, 2026 in Stem Cell Reports, represents a significant step toward a stem cell therapy for Type 1 diabetes that could make lifelong insulin injections obsolete.
An Immune System Gone Rogue
Type 1 diabetes develops when the immune system destroys the insulin-producing beta cells of the pancreas. Without insulin, body cells cannot absorb sugar from the blood, causing blood glucose to rise to life-threatening levels. Those affected must monitor their blood sugar throughout their lives and administer insulin multiple times daily, either by injection or through a pump.
According to the International Diabetes Federation Atlas 2025, around 9.5 million people worldwide are affected by Type 1 diabetes, an increase of 13 percent compared to 2021. Each year, approximately 3,000 children and adolescents under 15 receive the diagnosis in Germany alone.
Islet cell transplantation, where beta cells from donor organs are transferred, can cure diabetes. However, donor material is extremely scarce and patients must take immunosuppressants permanently, since their bodies would otherwise reject the foreign cells. These drugs weaken the immune system and substantially increase infection risk.
Three-Dimensional Self-Organization Solves an Old Problem
The team led by Prof. Fredrik Lanner from the Department of Clinical Sciences and Prof. Per-Olof Berggren from the Department of Molecular Medicine and Surgery at Karolinska Institutet developed a protocol that generates beta cells from human pluripotent stem cells. The decisive improvement over earlier attempts: the cells form three-dimensional clusters and largely organize themselves in the process.
This self-organization eliminates many unwanted cell types and improves the beta cells' ability to respond to glucose. Older protocols frequently produced immature cells that did produce insulin but failed to respond correctly to blood sugar changes. The new method solves exactly this problem, according to Lanner.
Particularly significant is that the protocol reproducibly works with eight different human stem cell lines, including four induced pluripotent stem cells (iPS cells) and four embryonic stem cell lines. Earlier methods often worked reliably on only one or two specific lines, limiting clinical transferability. "This opens possibilities for future patient-specific cell therapies that could reduce immune rejection," Lanner said in a press release from Karolinska Institutet.
In the mouse experiment, beta cells were transplanted into diabetic mice. The researchers used the anterior eye chamber as the transplantation site, which allows the development of the grafts to be observed directly over several months. The animals gradually restored their blood glucose regulation.
Vertex Is Further Along but Still Has the Immune Problem
The Karolinska work does not stand alone. US company Vertex Pharmaceuticals is considerably further along with its stem cell therapy zimislecel (formerly VX-880): in a small clinical trial with 12 patients with severe hypoglycemia unawareness, all 12 showed restored insulin production. Ten of the twelve patients required no external insulin after one year. The data appeared in The New England Journal of Medicine. Vertex has launched the Phase 3 FORWARD trial and plans an FDA submission for 2026, with a market launch of zimislecel possible no earlier than 2027.
The critical difference from the Karolinska approach: even with zimislecel, patients must take immunosuppressants permanently, because the stem cells do not come from the patient's own body cells. The Karolinska method aims in the long term to produce tailored beta cells from each patient's own iPS cells. This would theoretically bypass immune rejection.
A historical milestone is the so-called Edmonton Protocol from the year 2000: researchers in Canada transferred islet cells from donor organs into seven patients with Type 1 diabetes. All seven subsequently required no insulin. Long-term results were mixed, however: after five years, most patients had resumed insulin treatment, partly due to cell loss, partly due to side effects of the immunosuppressants. The Edmonton Protocol showed that a cure is possible, but not permanent and not without cost.
Three Hurdles Before the Clinic
Before the Karolinska method can be used clinically, three conditions must be met.
First, the protocol must be confirmed in larger animal models. Mouse studies are important proof-of-concept demonstrations, but diabetes in mice behaves differently from the human disease in several respects. Primate trials are the necessary next step before human studies.
Second, the immune question must be resolved. The theoretical advantage of patient-specific iPS cells is that the immune system recognizes the cells as belonging to the body and does not reject them. Whether this works in practice without any immunosuppression remains open. Type 1 diabetes arises from an immune system malfunction that attacks the body's own beta cells. This autoimmune program could also attack new beta cells derived from the patient's own stem cells.
Third, clinical trials are needed to demonstrate safety and long-term efficacy. This typically takes five to ten years. Prof. Lanner has announced plans to work toward clinical implementation, but Karolinska Institutet has not named a concrete timeline.