Scientists Reverse Diabetes in a Mouse Model Using Modified Blood Stem Cells


Source: Boston Children’s Hospital

Summary: Researchers have successfully reversed Type 1 Diabetes in a mouse model by infusing modified blood stem cells pre-treated to produce a protein which is deficient in Type 1 diabetic mice (and people).


In type 1 diabetes (T1D), autoreactive T-cells of the immune system attack islet cells specifically beta cells (which produce insulin) in the pancreas. Previous studies used immunotherapy techniques to treat T1D by curbing the autoimmune attack but the attempts were failed as the therapies did not target diabetes specifically. Researchers from Boston Children’s Hospital have successfully reversed Type 1 Diabetes in a mouse model by infusing modified blood stem cells pre-treated to produce a protein known as PD-L1 (Programmed death-ligand 1) which is deficient in Type 1 diabetic mice (and people). The blood stem cells curbed the autoimmune reaction in cells from mice and even humans and hyperglycemia was reversed in diabetic mice. The study findings were published in the journal Science Translational Medicine.

Type 1 diabetes treated through gene therapy

Researchers have successfully reversed Type 1 Diabetes in a mouse model by infusing modified blood stem cells. Credit: Andrea Panigada/Nancy Fliesler

Gene expression microarray was used to find the network of genetic regulatory factors (microRNAs) that control the production of PD-L1 is altered in blood stem cells of diabetic mice and humans. This prevents PD-L1 production even in the early stages of the disease. Researchers further showed that in context to type 1diabetes, PD-L1 has a potent anti-inflammatory effect. PD-L1 is an immune checkpoint, binds to the PD-1 receptor (inhibitory programmed death) on the T-cells that are activated to cause autoimmune reactions. This causes the T-cells to die or become inactive. The beauty of this approach is the virtual lack any adverse side effects as it uses patient’s own cells. Further study is needed to determine how long the cell therapy effects last and how often the treatment should be given. 

Senior investigator, Paolo Fiorina said, “Blood stem cells have immune-regulatory abilities, but it appears that in mice and humans with diabetes, these abilities are impaired”, “We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease.”


More Information: Ben Nasr et al, “PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes,”Science Translational Medicine (2017).

stm.sciencemag.org/lookup/doi/ … scitranslmed.aam7543


 

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