Modified Stem cells may cure Type 1 diabetes

It is estimated that about 5% out of 23.1 million people diagnosed with diabetes have Type 1. Beta cells located in the pancreas are responsible for producing insulin. In a normal person, beta cells sense elevated glucose levels and release the proper amount of insulin to lower sugar levels. In type 1 diabetics, the insulin producing beta cells are targeted by the body’s own immune system; however, new research has indicated that the inflamed response is caused by defective blood stem cells.

Researchers at Harvard Medical have shown that Type 1 diabetes can be stopped by increasing the levels of a one protein. They found that increasing the production of a protein called PD-L1 (Ligand for Programed cell death) in mice can reverse hyperglycemia (high blood glucose). Interestingly, PD-L1/PD-1 inhibitors are used in treatments for cancer. In a different study, a patient who was receiving PD-L1/PD-1 inhibitors for cancer was diagnosed with type 1 diabetes after taking the treatment for cancer.

One approach, bone-marrow transplant has shown promise, but is still not as effective as medical professionals had hoped. Thus, the purpose of the Harvard Medical research team was to identify why this autologous bone-marrow transplant may not always work. Attempting to find a cause to this dilemma, they used gene expression to discover the proteins that blood stem cells make, and noticed that the PD-L1 pathway in Type 1 diabetics is different to non-diabetics. They found that blood stem cells are defective in producing enough PD-L1 which halts the attack of T-cells (immune system) on beta cells. PD-L1 inactivates T-cells when it binds to another protein called PD-1 which sits on the surface of T-cells.

Furthermore, they treated blood stem cells to produce more PD-L1 and then tested them on human and mouse cells. Interestingly, they found a reduced inflammatory immune response in both human and mouse cells. They later injected the modified stem cells to diabetic mice and showed a reversal in hyperglycemia in the short-term, but in the long-term, a third of the of mice maintained normal sugar levels for the rest of their lives.

There are two ways these researchers modified the blood stem cells to produce more PD-L1. 1) They inserted a healthy gene for PD-L1 and, 2) they modified the cells’ protein machinery by mixing three small PD-L1 molecules into a cocktail. These two ways had the same outcome and reversed diabetic effects.

Paddock, C. (2017, November 17). Medical News Today. Retrieved November 19, 2017, from https://www.medicalnewstoday.com/

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