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Type 1 diabetes has been successfully reveresed in a mouse model by infusing blood stem cells pre-treated to produce more of a protein called PD-L1, which is deficient in mice (and people) with type 1 diabetes. The cells curbed the autoimmune reaction in cells from both mice and humans and reversed hyperglycemia in diabetic mice.

The study shows that the treated stem cells, given to mice, home to the pancreas where islet cells are made. Almost all the mice were cured of diabetes in the short term, and one third maintained normal blood sugar levels for the duration of their lives. The treatment was effective whether PD-L1 production was stimulated through gene therapy or pre-treatment with small molecules.

PD-L1 is known as an immune "checkpoint" molecule. It binds to the PD-1 receptor (inhibitory programmed death 1) on the inflammatory T-cells that are activated to cause autoimmune reactions. This causes the T-cells to die or become anergic (or inactive).

When Fiorina, Ben Nasr and colleagues introduced a healthy gene for PD-L1 into the stem cells, using a harmless virus as the carrier, the treated cells reversed diabetes in the mice. Fiorina and colleagues also found they could achieve the same effect by treating the cells with a "cocktail" of three small molecules: interferon beta, interferon gamma and polyinosinic-polycytidylic acid.

"We think resolution of PD-L1 deficiency may provide a novel therapeutic tool for the disease," Ben Nasr says.


More: https://www.sciencedaily.com/releases/2017/11/171115144126.htm

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