Reprogramming Stem Cells to Treat Type 1 Diabetes
Written By: Paphapin Pairojtanachai
August 27, 2020
A research study published in Nature on August 20th has shown that an international team including the University of Sydney has come up with a novel technique to reprogram induced pluripotent stem cells (iPS) into human islet-like organoids (HILOs) that can produce insulin — a hormone that promotes the absorption of glucose from the blood into liver, fat, and skeletal muscle cells — and control blood glucose levels. This serves as a potential new treatment for type 1 diabetes, which is an autoimmune disease in which the body’s immune cells mistakenly perceive the insulin-producing cells of the pancreatic islets as invading foreigners and destroy them.
Normally, one of the therapeutics for type 1 diabetes is a pancreas transplant, but this is typically reserved for patients who are severely affected by the complications of diabetes since getting a transplant could result in various other issues. For instance, the transplanted pancreas itself may be rejected by the immune system, causing the transplant recipients to have to take immunosuppressants, or drugs that lower the strength of the immune system’s activities, for the rest of their lives, which may bring about even more side effects. Otherwise, another remedy is for the type 1 diabetics to have a lifelong insulin replacement, which is often done by injecting or pumping insulin into the body.
Professor Chris Liddle, a principal investigator at the University of Sydney School of Medicine and a clinician at Westmead Hospital, informed that the stem cells used in the study came from the human umbilical vein and fat cells, and they were then reprogrammed to develop into HILOs. What’s interesting is that the team designed a “3D HILO” that doesn’t only consist of the insulin-producing cells of the pancreatic islets but also comprises other supporting cells found in the islets of Langerhans. Through the use of gene sequencing analysis and microscopic imaging, it can be seen that the 3D HILOs are very similar to the natural human islets. Thus, when these HILOs were placed in a 3D environment that mimics that of the pancreas and were “turbocharged with a ‘genetic switch’,” they were able to successfully produce insulin and regulate blood glucose levels in diabetic mice.
The major reason why the newly discovered method works is that the stem cells involved are able to stay in a patient’s body without being detected by the immune system. Ronald Evans, director of the Gene Expression Lab at the Salk Institute for Biological Studies, mentioned that “Normally, human cells placed in a mouse would be eliminated within a day or two. We discovered a way to create an immune shield that makes human cells invisible to the immune system.” In order to tackle the issue of immune rejection, the team of scientists focused on PD-L1, which is known as a protein that inhibits immune responses within the body. The team essentially modified the HILOs so that they would express PD-L1 and would hopefully be able to evade the body’s immune system. By doing so, the HILOs remained fully functioning in the diabetic mice for over 50 days, whereas the HILOs that were transplanted without PD-L1 gradually stopped working.
Although more research needs to be done among other animal models including primates before it can be tested in humans, this procedure definitely contributes an important step toward the cure for type 1 diabetes. As executive director Professor Philip O’Connell at The Westmead Institute for Medical Research who pioneered pancreatic islet transplantation in Australia almost 20 years ago says, “Stem cells derived from readily available human tissues can be expanded then re-programmed into potentially unlimited numbers of islets that are suitable for transplantation.”
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