Beta Invisibles
American scientists have created cells for the treatment of diabetes
Researchers from the American Salk Institute for Biological Research reported that they managed to create human cells that produce insulin and do not cause immune rejection during transplantation to patients with diabetes mellitus. The results of the study are published in the journal Nature (Yoshihara et al., Immune-evasive human islet-like organoids ameliorate diabetes).
Type I diabetes is a lifelong disease that is difficult to control even with the help of automatic devices that deliver insulin to regulate blood sugar levels. For decades, researchers have been looking for a way to replenish non-functioning pancreatic cells.
The solution could be a transplant of beta islets of the pancreas - clusters of cells that produce insulin and other hormones. But donor cells cause a rejection reaction and require patients to take immunosuppressants throughout their lives, which is associated with a serious risk of infections.
Using stem cell technology, scientists from the Salk Institute have created the first insulin-producing clusters of pancreatic cells capable of restoring glucose homeostasis without immune rejection after transplantation. Their effect has been successfully tested on diabetic mice.
"Most type I diabetics are children and teenagers. This is a disease that has historically been difficult to cope with with medication," the press release says. The words of the head of the research Ronald Evans, Head of the Department of Molecular Biology and Developmental Biology. "Now we hope that regenerative medicine combined with immune protection can really change the situation in this area by replacing damaged cells with clusters of human islets created in the laboratory, which produce normal amounts of insulin at the request of the body."
In a previous study, the authors have already managed to create beta-like cells from stem cells. These cells had the ability to produce insulin, but they didn't have enough energy for it. Subsequently, scientists discovered a genetic switch called ERR-gamma, which "charges" cells when turned on.
"When we add ERR-gamma, cells get the energy they need to do their job," says another study author Michael Downes, a senior researcher at the Salk Institute. "These cells are healthy and strong and can deliver insulin when they feel high glucose levels."
The most important part of the new study was the development of a method for growing three-dimensional islands of beta-like cells, similar in shape to the human pancreas. As a result, scientists received the so-called HILO human islet-like organoids, ready for transplantation.
To protect against immune rejection, the authors used the checkpoint protein PD-L1, used in a number of immunotherapeutic drugs against cancer.
"By expressing PD-L1, which acts as an immune blocker, the transplanted organoids can hide from the immune system," explains the first author of the paper, Eiji Yoshihara, a former employee of the Salk Institute's gene expression laboratory.
Yoshihara developed a method for inducing PD-L1 in HILO by short pulses of interferon gamma protein.
"This is the first study showing that it is possible to protect HILO from the immune system without genetic manipulation,– Downs emphasizes. "If we can formalize this as therapy, patients won't need to take immunosuppressants."
The authors note that before bringing the system to clinical trials, additional studies need to be conducted. In particular, transplanted organoids need to be tested on mice for longer periods of time to confirm their long-lasting effect and guarantee safety for humans.
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