Researchers at Boston Children’s Hospital successfully reversed Type I diabetes in a mouse model using blood stem cells, according to a study published this week in Science Translational Medicine.
The researchers used cells that were pre-treated to make more of a protein, PD-L1, which is deficient in mice and people with Type I diabetes.
“There’s really a reshaping of the immune system when you inject these cells,” senior investigator Dr. Paolo Fiorina said in prepared remarks.
Researchers have tried before to use immunotherapies in an attempt to stop the body’s attack on its own islet cells. Efforts to reboot a patient’s immune system by infusing them with their own blood stem cells has helped some patients, but not all of them.
The team at Boston Children’s Hospital said that previous attempts have failed because the therapies do not specifically target diabetes.
“Blood stem cells have immune-regulatory abilities, but it appears that in mice and humans with diabetes, these abilities are impaired,” Fiorina explained. “We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease.”
The team discovered that the genetic regulatory factors responsible for production of PD-L1 are different in blood stem cells from diabetic mice and people, which ultimately stops the production of PD-L1.
PD-L1 binds to the PD-1 receptor on inflammatory T-cells that are triggered to cause autoimmune reactions, the researchers found. When PD-L1 binds to the PD-1 receptor, the T-cells die or become inactive.
The team reported that when they added a healthy gene for PD-L1 into the blood stem cells, the cells reversed diabetes in the mouse model.
They also achieved the same results by treating the cells with a mix of three small molecules.
“We think resolution of PD-L1 deficiency may provide a novel therapeutic tool for the disease,” first author Moufida Ben Nasr said.
The researchers have teamed up with San Diego, Calif.-based Fate Therapeutics to optimize the small-molecule cocktail used to treat the blood stem cells before infusion. They have met with the FDA for a pre-IND meeting in preparation for a clinical trial in patients with Type I diabetes, the team reported.