Health
Immune escape cells with PD-L1 control diabetes in mice
Generating insulin-producing pancreatic beta cells from stem cells to replace those destroyed by the immune system is a promising approach to treating diabetes. However, responding to changes in glucose and preventing immune attack after the cells have been transplanted has proven difficult.
Now, scientists at the Salk Institute have found potential solutions to these problems. They created functional 3D cell clusters, called human islet-like organoids (HILO), that restore glucose control in a mouse model of diabetes without causing immune rejection. Nature..
The team successfully protected HILO from the immune system without genetic manipulation. If this approach is a successful treatment, teams may say that patients who receive islet transplants may be able to avoid the need for chronic immunosuppression, which may increase the risk of potentially dangerous infections. Suggested.
Formerly Soak Researcher discovered Increased expression of a receptor called ERR-gamma provides beta-like cells derived from human induced pluripotent stem cells (iPSCs) with sufficient energy to mature into functional cells that respond to glucose changes by producing insulin. May be given.
In a new study, researchers found that a protein called WNT4 could turn on ERR-γ driven maturation of beta cells. They used that pathway to build mature cells and create HILO in a 3D environment that mimics the human pancreas.
To address the complex issues of immune rejection, including autoimmune reactions, the team has taken up the popular Cancer Immunotherapy page.
We found that a subset of healthy islet cells express PD-L1, a known checkpoint that suppresses immune responses. To investigate whether PD-L1 expression protects HILO from immune rejection, the team generated two types of HILO.
Researchers at Salk have developed a method to induce PD-L1 in HILO using repeated short-term exposure to the protein interferon gamma. The team reported that these HILO reduced glucose levels for more than 40 days when transplanted into diabetic mice with a healthy immune system, but reduced the efficacy of cells lacking interferon-gamma treatment.
Relation: How existing drug cocktails regenerate insulin-producing cells in diabetes
Scientists have long sought a way to overcome the obstacles of immune rejection in transplanting islets to treat diabetes. Georgia Institute of Technology, Louisville University, University of Michigan Team Conceived They showed a hydrogel containing the protein Fas ligand, which was able to “educate” immune cells to accept foreign islands.
The lack of high quality islet donors has also prompted efforts to use stem cells to generate beta cells. Sigilon Therapeutics continues to work with diabetic giant Eli Lilly, developing iPSC-based encapsulated beta cell therapy. Massachusetts Biotechnology has recently raised $80 million in Series B funding.
Researchers at Salk plan to test HILO implants in mice for extended periods to confirm their efficacy and safety before starting clinical trials. “This is the first study to show that HILO can be protected from the immune system without genetic manipulation,” said study co-author Michael Downs. Said In a statement. “If this could be developed as a treatment, patients would not have to take immunosuppressive drugs.”
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