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Home > News & events > News > Transplanted beta cells avoid immune attack in mice with type 1 diabetes
A photo through a microscope of the non-engineered (left) and engineered (right) human islets, which contain different hormone producing cells including beta cells. Different hormones are labelled in different colours: green is insulin, red is glucagon and blue is somatostatin.
Genetically engineered beta cells transplanted into mice with type 1 diabetes avoid immune system attack and stabilise blood glucose levels without immunosuppressants.
Researchers from Sana Biotechnology in California took pancreatic islets (clusters of cells in the pancreas) from human donors and took out the insulin-producing beta cells inside them. Next, they genetically engineered these beta cells so the immune system can’t find them. They did this by removing the markers on the surface of the cells that immune cells can detect. Then the researchers let the genetically modified beta cells recombine with the other pancreas cells into islets again.
The researchers transplanted three hundred islets into the leg muscles of each mouse with type 1 diabetes. They gave some mice human islets containing the genetically engineered beta cells and gave others human islets which they hadn’t changed. The scientists watched what happened to the beta cells over the next month.
The islets containing non-engineered beta cells were fully rejected and destroyed by the mice’s immune system over seven to 10 days. In these mice, the transplanted cells had no effect on the animals’ blood glucose levels, and the mice had no c-peptide (a measure of insulin) after one month.
Meanwhile, all the genetically engineered beta cells survived for the entire month without being attacked by the immune system. They also connected with their blood supply and stabilised the mice’s blood glucose levels after just two weeks.
Before any treatment can be tested on people in clinical trials, they must first be given to animals in tests called preclinical trials. This is to ensure we only test the safest and most effective therapies on humans to lower any potential risks. The mice the researchers used had type 1 diabetes and were ‘humanised’, meaning they had human immune cells instead of mouse immune cells. Also, the islets the researchers transplanted were from humans. Both these features make the study as relevant to people with type 1 as possible.
Currently, islet transplants containing functioning beta cells from pancreas donors only last around five years before the immune system attacks them again. For this reason, the recipient needs to take immunosuppressant drugs, which increase their risk of infection and cancer. Lots of these transplanted islets are immediately destroyed by the immune system because it detects that they are not the recipient’s own cells. Those that survive are gradually destroyed by the autoimmune attack which destroyed the person’s original beta cells. For islet transplants to be more successful, we need to stop the immune system destroying them. The researchers in this study have achieved this by genetically engineering beta cells so that the immune system can’t find them.
These genetically engineered beta cells from human pancreases were more effective than the beta cells which have, so far, been grown in a lab from stem cells. These beta cells released insulin in response to rising glucose levels more effectively than the beta cells that researchers can currently grow in the lab. Find out more about our research on lab-grown beta cells.
Another advantage is that the beta cells used in this study didn’t require immunosuppressant drugs. The lab-grown beta cells currently being tested in clinical trials do need the recipient to take immunosuppressant drugs, although researchers are working hard to genetically engineer lab-grown beta cells to avoid the immune system attack, in a similar way to those used in this study.
The exciting results from this research project demonstrate a potential cure for type 1 diabetes. The researchers are waiting for the results from another clinical trial where non-engineered donor islets are being transplanted into people’s arm muscles. If this proves successful, they will design a clinical trial to transplant their genetically engineered islets into the arm muscles of people with type 1.
Access the full research paper at the Science Translational Medicine website.
The research, which was co-funded by JDRF, reveals that drugs that target the immune system offer very effective and rapid improvements in stabilising blood sugar levels, often within just three months.
The new JDRF-funded clinical trial called SOPHIST will test a drug to help people with type 1 diabetes and heart failure.
Results from a clinical trial called the PROTECT study show that teplizumab can preserve beta cell function in children and adolescents newly diagnosed with type 1 diabetes.
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