The transplantation of missing cells to type 1 diabetic without risk of rejection is already possible in mice, according to new research. With the help of stem cells, scientists have created insulin-producing cells that can go unnoticed by the patient’s immune system.
This is a huge step forward in diabetes treatment that scientists have achieved. In the laboratory, researchers have recreated Langerhans cells, the pancreatic cells that produce insulin and whose malfunction is the cause of the disease. It is even better that these organoids are modified to evade the immune system so that they can be transplanted without the risk of rejection. This method has been successfully tested on diabetic mice according to an article published in Nature.
Type 1 diabetes is treated by daily injections or transplants from deceased donors
While type 2 diabetes usually occurs in adults, type 1 is an autoimmune disease that occurs most frequently in childhood or adolescence. The core of the problem lies in the pancreas, where insulin-producing cells are slowly destroyed. Without islets of Langerhans, glucose (sugar) can no longer be stored properly in the body’s cells. This leads to hypoglycemia and long-term risk of stroke, heart attack, kidney failure, and coma.
To provide the missing insulin, most patients undergo daily insulin injections. Some have benefited from islet cell transplants from deceased patients. But as with all transplants, this technique requires a lifetime of immunosuppressive drugs to prevent the immune system from rejecting the transplant, which increases the risk of infection. This is where Prof. Ronald Evans’ team project comes in at the Salk Institute in San Diego.
Cells that can evade the immune system
With the help of stem cells that can be transformed into any cell in the body, researchers were able to reproduce very special islets of Langerhans, called HILO (for “human islet-like organoids”), in the laboratory and in three dimensions. The cells that make them up are in fact genetically modified in such a way that they produce insulin on demand according to the levels of glucose detected in the body, just like real insulin, without being rejected by the recipient organism.
The first modification concerns ERR-gamma. “When we add ERR-gamma, the cells have the energy to do their job,” says Michael Downes, co-author of the study, in a statement. “These cells are healthy and robust and can release insulin when they detect high glucose levels.
The second genetic modification allows cells to remain undetectable by the immune system. This method is inspired by the method used for some types of cancer. Thanks to it, cells are able to produce a protein called PD-L1 at the right time, which acts as a “stop” sign in front of the white blood cells that can recognize it. The signal produced by this PD-L1 is a molecule produced by the immune system that allows HILOs to lift the shield at the right time. “By expressing PD-L1, which acts as an immune blocker, transplanted organoids are able to hide from the immune system,” explains Eiji Yoshihara, the lead author of the study. As a result, HILOs without PD-L1 gradually lost their effectiveness in diabetic mice, while HILOs with PD-L1 successfully controlled blood glucose levels for 50 days!
A procedure that will most likely be too expensive
More research needs to be done before clinical trials can be done. In particular, longer tests on mice will make it possible to check the duration of action of transplanted organoids. It will also be necessary to ensure that they can be used safely in humans. If this work leads to a cure, the lives of millions of diabetics could be changed. “We now have a product that can be used on patients without the need for a device,’ concluded Professor Evans. However, removing the patient’s cells, regressing them to obtain stem cells, and then modifying them to create a custom-made transplant would be a very costly process. For this reason, researchers suggest that transplants from compatible donors, modified to escape the immune system, could be a future middle of the road solution.