Uppsala's world first: islets the immune system ignores
In 2025 a team in Uppsala showed that gene-edited islet cells can survive in a person with type 1 diabetes without immunosuppression. What was done, what it shows, and what Sweden needs for the next step.
At Uppsala University Hospital (Akademiska sjukhuset), a 42-year-old man who had had type 1 diabetes for 37 years received gene-edited donor islet cells in his forearm muscle. He got no immune-suppressing drugs. Fourteen months later the cells were still alive and making insulin, and his immune system hadn’t attacked them.
No one had shown that before. It’s the single most important result so far for a cure without immunosuppression.
What was done
The study, UP421, is led by Per-Ola Carlsson, professor and senior physician in Uppsala, and run together with Sana Biotechnology, the US company that owns the gene-editing approach. It’s a first-in-human study with one patient.
The donor islets were edited with Sana’s “hypoimmune” method:
- HLA class I and II removed. These are the molecules T cells use to recognise cells as foreign. Without them, the cells give T cells nothing to react to.
- CD47 increased. Cells without HLA would normally be destroyed by other immune cells (natural killer cells and macrophages). CD47 tells those cells not to.
The cells were injected into forearm muscle rather than the liver. There the graft can be followed with PET-MRI scans, and it’s easy to reach.
What it shows
From the NEJM paper (2025) and the follow-up letter (2026):
- The edited cells survived, made insulin in response to meals, and triggered no immune response, from either rejection or the original autoimmunity.
- At 14 months, C-peptide (a measure of the body’s own insulin) was comparable to the first six months, and the graft was still visible on PET-MRI.
- Not every cell in the graft was fully edited. In lab tests of the patient’s blood, cells that still carried HLA were attacked by T cells and antibodies, and cells without HLA but with normal CD47 were killed by other immune cells. The fully edited cells were spared. That shows his immune system was active, and that both edits were needed.
- There were no serious side effects linked to the treatment.
What it doesn’t show
- It isn’t a cure, by design. For regulatory reasons the dose was intentionally low: about 7% of what is expected to make someone insulin-free. The patient still uses insulin; his dose was even raised after the transplant to protect the graft.
- It’s one person. Survival in one patient is a proof of principle, not a measure of how often it works.
- The cells came from donors. Donor islets can’t treat millions of people. The scalable version, the same edits in stem-cell-derived islets, is Sana’s SC451, and it isn’t in a trial yet.
Uppsala’s strengths, and what’s missing
Uppsala has the clinic, the result and long experience. Akademiska has done more than 170 islet transplants in about 60 patients since 2001.
What’s missing is large-scale production of stem-cell-derived cells. The edited cells for UP421 were prepared at Oslo University Hospital, within the Nordic network for clinical islet transplantation. In November 2025 the research group said that the next study needs cell production at scale, and that access to cells is a precondition.
There are steps toward it:
- ATMP Center Uppsala, formed in 2023 for advanced therapies, plans its own GMP-certified production unit and has agreed to work with Karolinska on advanced therapies.
- Stiftelsen för typ 1-diabetesforskning, a foundation started in 2025 by two parents of children with type 1 diabetes and managed by Uppsala University, funds the work and accepts donations. The group has said it could help start the next study within two to three years.
The wider context matters too. Novo Nordisk, the Nordic region’s largest player in stem-cell islets, closed its cell-therapy unit in October 2025 and passed the program to a Canadian company. And Uppsala’s next step depends on Sana, a company whose latest report raises doubt about its ability to continue without new money. The science is ahead of the funding.
What to watch
- Sana’s application to start the SC451 trial, which it expects to file “as early as” the end of 2026.
- Whether a trial site in Europe, possibly Uppsala, is part of it.
- Longer follow-up of the UP421 patient.
- Funding for GMP cell production in Sweden.
The trial facts were checked against the publications on the date above. Facts about Uppsala’s infrastructure come from the linked sources from 2025.