Nature: Heavy! For the first time, a human islet-like cell cluster with immune avoidance has been developed and is expected to be used to treat type 1 diabetes.

August 26, 2020 /--- estimated that type 1 diabetes affects 1.6 million Americans and costs $14.4 billion a year.
a new study, researchers from the Shack Institute of Biology in the United States have made significant progress in pursuing safe and effective treatments for type 1 diabetes.
using stem cell technology, they produced for the first time a cluster of human insulin-secreted pancreatic cells that evade the immune system.
these "immune shielded" cell clusters are transplanted into the body, no immunosuppressive drugs are needed to control blood sugar.
results were published online August 19, 2020 in the journal Nature under the title "Immune-evasive human islet-like organoids ameliorate diabetes".
images from the Salk Institute.
type 1 diabetes are children and adolescents," said Professor Ronald Evans of the Shack Institute of Biology and co-author of the paper.
is a disease that has historically been difficult to control with drugs.
We want regenerative medicine to work in this area by replacing damaged cells with laboratory-generated islet-like cell clusters and producing a normal amount of insulin on demand."
type 1 diabetes is a challenging lifelong condition that is difficult to control even when automated devices are used to deliver insulin to regulate blood sugar.
transplanting islets from the provider's tissues ---cellular clusters that make insulin and other hormones--- can provide a cure, but there is a serious risk that patients will need to take immunosuppressive drugs for life.
for decades, scientists have been looking for a better way to replenish lost pancreatic cells.
, according to Evans Labs, today's deviceless transplants of insulin secretion cells like this bring us one step closer to curing the disease.
previous study, Evans' lab overcame an obstacle in the field: beta-like cells produced by stem cells produce insulin, but are not functional.
, said the cells did not release insulin to cope with glucose because they were under-motivated.
team discovered a gene switch called ERR-gamma that, when turned on, "turbo-charge" the cells.
when we add ERR-gamma, these cells have the energy they need to get the job done," said Michael Downes, a senior scientist at the Shack Institute of Biology and co-author of the paper.
these cells are healthy and robust, providing insulin when they feel high glucose levels.
a key part of the new study is the development of a way to grow beta-like cells in a three-dimensional environment similar to the human pancreas.
these cells have islet-like properties.
, the team found that a protein called WNT4 turns on a mature switch driven by ERR-gamma.
combination of these steps has resulted in functional clusters of cells that simulate human islets: so-called human islet-like organoids (HILO).
, the team solved the complex problem of immune rejection.
normal tissue transplants require lifelong immunosuppressive therapy to protect the tissue from the immune system;
inspired by the success of cancer immunotherapy drugs, the team initially found that checkpoint protein PD-L1 protects transplanted cells.
, lead author of the paper, said, "By expressing PD-L1, which works as an immune blocker, transplanted organ cells can evade the immune system."
", Yoshihara developed a method of inducing PD-L1 expression in HILO in a short period of time using interferon gamma.
when transplanted into diabetic mice, these immune-shy HILOs provided continuous blood sugar control in diabetic mice with a healthy immune system.
, "This is the first study to show that you can protect HILO from the immune system without genetic action, " explains Downes.
if we could develop it as a therapy, patients would not need to take immunosuppressive drugs, " he said.
more research is needed before the system can be advanced to clinical trials," he said.
transplanted organs need to be tested longer in mice to confirm that their effects are long-lasting.
more research is needed to ensure that they can also be used safely in humans.
Now we have a product that has the potential to be used in patients, and possibly in patients without any equipment, " says Evans.
" (bioon.com) Reference: 1. Eiji Yoshihara et al. Immune-evasive human islet-like organoids ameliorate diabetes. Nature, 2020, doi:10.1038/s41586-020-2631-z.2.First immune-evading cells created to treat type 1 diabetes.