Uppsala University researchers report that they have made a significant step forward in the journey to cure type 1 diabetes. Using genetically engineered pancreatic cells, the scientists say they have finally found a way to prevent a patient’s immune cells from destroying transplanted islet cells without employing immunosuppressive drugs. Could we be seeing routine pancreatic cell transplants for type 1 diabetes soon?
Pancreatic cell transplants for type 1 diabetics without immunosupressive drugs
In a study published in the New England Journal of Medicine August 2025, the team led by Per-Ola Carlsson, M. D., Ph.D. and Sonja Schrepfer, M. D., Ph.D. describes how they solved the perennial pancreatic problem that has blocked progress in developing regenerative treatments for type 1 diabetes. The researchers took donated pancreas cells and reprogrammed them to deactivate immune cell-attracting proteins.
The doctors then surgically implanted them into a man with type 1 diabetes and watched to see whether the man’s immune system would notice and attack the transplanted cells. Encouragingly, these genetic tweaks appeared to protect the cells for twelve weeks, until the experiment ended.
In this case report, the researchers did not permanently cure the patient’s type 1 diabetes; they did, however, make a huge leap forward. They have shown that this approach passes the first two hurdles: firstly, insulin-producing cells survive the process of genome editing and still make a good amount of insulin; secondly the genome editing was successful in camouflaging the cells for at least three months. The next steps will be to figure out how many cells need to be implanted to make enough insulin to compensate for their diabetes and to find out how long the cells last once implanted.
Type 1 Diabetes: No Bed of Roses
Type 1 diabetes is caused by the death of specialized insulin making cells, known as islet cells, inside your pancreas. If you don’t have islet cells in your pancreas, you can’t produce your own insulin. This means that type 1 diabetics must carefully control their blood glucose levels using insulin injections. Type 1 diabetes is a life long condition that, unlike type 2 diabetes, cannot be reversed. Once your islet cells are gone, they are gone for good.
Islet cells gained their name because when you slice up a pancreas, you find that it’s dotted with roughly circular structures called ‘islets of Langerhans’. The clumps of cells clustered together in these islets are insulin-making cells and glucagon-secreting cells.
Insulin tells your body to store glucose for later, and glucagon tells your body to release glucose into your blood when you need energy. You need both insulin and glucagon-producing cells to keep the amount of glucose in your blood in balance. People who do not have insulin-making cells need to measure their blood sugar carefully and give themselves doses of insulin via injection or pump throughout the day. So why don’t type 1 diabetics automatically get put on the list for a pancreas transplant?
Why not transplant? It’s complicated
There are a few wrinkles that make pancreas transplants for type 1 diabetics impractical as a routine treatment. Firstly, the number of folk who would need a transplant is huge. In 2025 the International Diabetes Federation put the number of people worldwide who have type 1 diabetes at 9.5 million, with as many as 513,000 new cases each year. Secondly, an organ transplant recipient will need to take immunosuppressive drugs for the rest of their life.
Immunosuppressive drugs are a marvel that have helped people with immune disorders, such as lupus, live more comfortably and have made donated organ transplants possible. The problem with immunosuppression is that we need our immune systems to protect us from infectious diseases and cancer.
Immunosuppression makes people more vulnerable to infections; it can allow cancers to develop. Some drugs have side effects that can cause cardiovascular illnesses, kidney disease and neurological problems. Some classes of immunosuppressants can even trigger insulin resistance – the opposite of what you want for a diabetic recipient. These side effects are worth it in many situations, but for the average parent making a decision about treating their child’s type 1 diabetes, managing their condition with insulin would be the most affordable and practical option.
Another avenue would be to use a person’s own stem cells to regenerate the missing insulin producing islet cells. This is the holy grail of regenerative medicine. The idea of avoiding all the problems of transplant rejection and immunosuppressants by growing cells in a dish and implanting them into the right part of the body drives countless research programs worldwide. Islet cells are a great candidate for this approach – in theory.
Islet Cells Wanted: Dead or Alive
So why can’t doctors use stem cell therapy yet? In short, it’s because type 1 diabetes is usually an autoimmune disease. immunologists theorize that our immune system mistakes our islet cells for pathogens.
This might happen because a person has a DNA mutation that makes their islet cells look ‘not right’ to white blood cells. Or perhaps a lot of islet cells die because of an injury or infection, and the immune system confuses the proteins released by the dying cells for toxins and marks cells that make them as dangerous. Another possibility is that a very nasty viral infection can overwhelm the immune cells, causing them to muddle up the normal parts of the infected cells with pieces of virus.
This means that any time something that looks like an insulin-making islet cell turns up in their body, their immune system will kill it.
Bad Medicine
More than 90% of people diagnosed with type 1 diabetes have genetic mutations in one or more of two specific components of the cell’s defence system. The proteins encoded by the genes are HLA-DR3 and HLA-DR4. These Human Leukocyte Antigen (HLA) proteins sit on the surface of cells in the pancreas. Usually, if a cell gets infected with a virus or turns cancerous, the cell will chop up bits of any problematic proteins and use its HLA proteins, like a display stand on the outside of the cell.
This alerts patrolling lymphocytes (infection busting immune cells) to the issue, and signals that they need to destroy the cell. It looks like the HLA-DR3,DQB10201 and HLA-DR4,DQB10302, variants of the HLA genes have an error that triggers immune cells to activate even if they aren’t holding a chunk of virus or cancer marker.
It’s a bit like if you tried to report a lurker caught on your ring camera, and, in the process, accidentally uploaded a photo of yourself to the FBI’s most wanted list.
The upshot is that eventually the immune system labels the islet cells of the pancreas as a threat and targets them for death. This means that any attempt to grow new islet cells in the pancreas fails. Without immunosuppression you can’t use pancreatic stem cells from your own body; you can’t use stem cells from other parts of your body to make islet cells and you definitely can’t transplant someone else’s pancreas.
Keep the Faith
Carlsson and colleagues used a devastatingly clever way to get round this problem. They reasoned that the donated cells can’t trigger an immune response if they can’t build the antigen display complex. This would allow implanted islet cells to survive in a diabetic’s body, restoring their ability to create their own insulin, and all without the need for immunosuppressants.
They would remove the HLA genes that attract the islet cell killing T – Cells and they would add a gene that repels the Natural Killer Cells and macrophages that kill cells with no HLA proteins.
The team planned to implant these genetically engineered cells in a type 1 diabetes patient. If all went well, they hypothesized, the transplanted islet cells would survive and secrete insulin. After all, they had tried it before in various animal models with success.
A 42-year-old man who had had type 1 diabetes since the age of five volunteered to be a guinea pig. This patient had no ability to make his own insulin and he had antibodies that attack islet antigen 2 – confirmation that autoimmunity was the cause of his diabetes. A perfect subject for this crucial proof of concept experiment.
Their strategy was to find a donor who was a good match to the participant so that they could minimize the immune response to the foreign cells. They would collect the pancreas, isolate islet cells and use CRISPR/Cas 12b to edit their genomes to remove the HLA genes. They would then implant the genetically engineered cells into the patient. Once implanted with the cells, the team would monitor his immune responses over 12 weeks and check whether the implanted cells could still make insulin.
Could they outwit his islet cell-attacking immune system?
Isl’et be there for you
Doctors collected pancreatic islets from a 60 year-old a type 0 negative donor with a healthy pancreas. They tested the islets to make sure they produced insulin effectively, and sent the best islets to the lab for gene editing.
Once the scientists had the islets, they isolated single islet cells into a flask and added special lipid coated DNA encoding molecular scissors and guide RNAs designed to target the B2M and CIITA genes. These genes are the blueprints for parts of the HLA complex.
After they had given the DNA time to soak into the cells and recover, they used genetically engineered virus to transfer an extra copy of the CD47 gene into the cells to prevent other immune cells from targeting them.
In These Arms
Next, they tested the cells to see how well the gene editing worked. Using flow cytometry, they sampled a representative specimen of the engineered cells. They found that 85.8% of the cells had lost the ability to make class I HLA complexes and 100% could no longer make class II HLA complexes. Around 46% of the cells were making extra CD47 proteins. Importantly, they detected no evidence that the cell culture and gene editing methods had changed the characteristics of the cells or the proportions of different subtypes of cells.
The cells were a mix of various combinations of the genetic treatments. A small number of cells were normal ‘naïve’ islet cells. In some cells only class II HLA was turned off; some cells had a disabled class II HLA and extra CD47 proteins. The majority of cells made neither HLA class I nor class II, with half of those also expressing addition CD47.
The researchers then sent the flasks to the clinic. Doctors injected 79.6 million genetically engineered islet cells into the patient’s left forearm.
They did not give the patient any glucocorticoid steroids, anti-inflammatory drugs or immunosuppressants.
Never Say Goodbye
For the next twelve weeks, the researchers and the participant met regularly to monitor the implanted cells. Each visit, the team would test to see whether the islet cells had triggered an immune response and if they were still there and making insulin.
Within a week, the implanted cells that still had both HLA class I and II proteins had triggered an immune response. T cells had recognized them as islet cells and started to kill them off. They also found IgM antibodies that signify an infection – meaning the participant’s immune system was treating these implanted cells like a new infection. After three weeks this antibody response had switched to an IgG response, meaning his immune system recognized them as common pathogens. At every check-up, these naïve cells were being attacked by both the innate and adaptive immune system.
The engineered cells with neither class I nor II HLA genes were killed off by the innate immune system’s Natural Killer cells and macrophages pretty quickly, unless they were carrying the extra CD47 gene. The adaptive immune response did not affect these cells.
The cells with the full set of three genetic tweaks fared the best. They avoided both the adaptive and innate immune system, allowing the cells to survive for the 12-week observational period.
In and out of Insulin
When it came to insulin production, the results were not bad at all. For the first few weeks, they didn’t do much; by week 12, the doctors noticed a very good sign. Before the treatment, the man had no measurable C peptide in his blood after a meal. This means he was not making any insulin.
By week 12, however, C peptide measurements rose after a meal, indicating that the implanted cells were sensitive to changes in blood glucose and they could make insulin. The man was also using his regular insulin regimen, but the implanted cells were helping.
The experiment continues as of 2025. The researchers will follow up to see how long the implanted cells survive, how long they continue to make insulin and whether the cells stay where they should.
Get Ready for Pancreatic cell transplants for type 1 diabetes
The key take away from this case report is that Swedish researchers have developed a way to implant pancreatic cells into a type 1 diabetic without them being attacked by the patient’s immune system. This is the first tangible step towards human pancreatic cell implants. Doctors have been trying to transfer living islet cells to cure diabetes since the 1950s with very little progress.
The other important finding is that the donor pancreas cells were from another person. Normally, these cells would have been firmly rejected by the recipient’s body unless he was regularly taking immunosuppressant drugs. In this case, however, the deletion of the two HLA proteins allowed the donor cells to survive without immunosuppressants or anti-inflammatory drugs. This opens a new path for donor-recipient cell transplants that would normally be too difficult to attempt. As far as islet cell transplants go… watch this space.
Read the full report in NEJM:
I really have to applaud the writer/editor’s commitment to Bon Jovi crossheads. Well done (from one journo to another).
Ha! Thanks!