1型糖尿病,人类胰岛样细胞簇 z-bo 2020-10-07 313

　　Type 1 diabetes affects 1.6 million Americans and is estimated to cost $14.4 billion annually. In a new study, researchers at the Shaq Institute of Biology in the United States have made great strides in pursuing safe and effective treatments for type 1 diabetes. They used stem cell technology to create a cluster of human insulin-secreting pancreatic cells that can evade the immune system.

　　These "immune shielded" cell clusters are transplanted into the body to control blood sugar without immunosuppressive agents. Professor Ronald Evans of the Shaq Institute of Biology said: “Most people with type 1 diabetes are children and adolescents. This is a disease that has historically been difficult to control with drugs. It is produced in the laboratory. Human pancreatic islet-like cell clusters replace damaged cells. The combination of avoiding and producing normal amounts of insulin as needed has indeed played a role in this field. This is a challenging lifelong disease to regulate blood sugar levels. Even if used Automated equipment to deliver insulin is also difficult to control. Transplanting islets from donor tissue (clusters of cells that make insulin and other hormones) can provide treatment, but patients will have to take immunosuppressive drugs throughout their lives and bring serious risks. Scientists are always looking for better ways to replace the lost pancreatic cells. According to this report, this device-free transplantation of insulin-secreting cells is close to today’s treatment of diseases. In previous studies, the Evans Institute Overcoming obstacles in this field through stem cells. The β-like cells produced produce insulin but have no function. Evans said that these cells do not have enough energy to release insulin in response to glucose. His team discovered a type called ERR- The genetic switches of gamma are “turbocharged” when they are turned on. The co-author of this paper, Michael Downs, a senior scientist at the Shaq Institute of Biology, said: “By adding ERR-γ, these cells have The energy required to complete the task. These cells feel healthy and strong. At high glucose levels, they can provide insulin. "

　　An important part of this new research is the development of methods to grow β-like cells in a three-dimensional environment similar to human pancreas. This makes these cells have properties similar to pancreatic islets. Importantly, the research team discovered that a protein called WNT4 can turn on a maturation switch driven by ERR-γ. The combination of these steps produces functional cell clusters that mimic human islets, so-called human islet-like organoids (HILO).

　　Next, the research team solved the complex problem of immune rejection. Normal tissue transplantation requires lifelong immunosuppressive therapy to protect the tissue from the immune system, but these therapies also increase the risk of infection. Inspired by the success of cancer immunotherapeutics, the research team first discovered that the checkpoint protein PD-L1 can protect transplanted cells. The lead author of the paper, Eiji Yoshihara, said: “By expressing PD-L1 as an immune blocker, transplanted organ cells can evade the immune system.”

　　After, Yoshihara Hara produced short-term induction of HILO through interferon gamma. PD-L1 expression method. When transplanted into diabetic mice, these immune-evasive HILOs provide continuous blood sugar control in diabetic mice with healthy immune systems.

　　Downs explained: “This is the first study to show that HILO can protect the immune system without genetic manipulation. If it can be developed as a treatment, patients do not need to be immunosuppressed.”

　　Before the clinical trials of this system are conducted, further research is needed. Such transplanted organoids should be tested for a long time in mice to ensure that their effects persist. More research work is needed to ensure that they are safe for humans. Evans said: "Now, we have a product that can be used by patients. It can be used by patients without equipment."