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Diabetes: Protein gels may help treat type 1 diabetes by preventing transplanted pancreatic cells from being rejected

Gels transplanted in parallel with islet cell transplantation in type 1 diabetic monkeys release proteins that kill excess immune cells and prevent pancreatic cells from being rejected.


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May 13, 2022

Microscopic image of microgel with protein Fas ligand on the surface

Esma Jörg

Transplanting pancreatic cells with protein-releasing microgels has improved Diabetes mellitus Without monkey control Transplant Rejected cell.

Who has Type 1 diabetes Their immune system mistakenly attacks the islet beta cells of the pancreas, which normally produce the hypoglycemic hormone insulin, so insulin must be infused to regulate blood sugar levels. Transplanting islet beta cells from a deceased donor allows people with type 1 diabetes to produce their insulin, but recipients need lifelong immunosuppressive drugs to prevent the cells from being rejected. .. This weakens their immune system and increases the risk of infections and cancer.

Looking for an alternative treatment, Gilley Harvard Medical School and his colleagues injected seven monkeys with a natural drug called streptozotocin that kills islet beta cells to induce type 1 diabetes. Twelve days later, scientists removed the islets from healthy monkeys and mixed them with microgels. The cells and microgels were then transplanted into the abdominal panniculus of the monkey.

Four of the monkeys received a microgel filled with Fas ligand (FasL), a natural protein that kills overactive immune cells, and a protein called streptavidin (SA) that “glues” FasL to the microgel. By pre-mixing the gel with islet cells, the gel slowly releases FasL to the cells once transplanted into the body and prevents them from being rejected.

The remaining three monkeys received islet transplantation with “empty” microgels without FasL or SA. All seven monkeys received insulin supplementation for the first 28 days and the rejection inhibitor rapamycin for 3 months.

For the next six months, monkeys treated with SA-FasL microgel produced the same levels of insulin as they did before developing diabetes, at least on an empty stomach, according to researchers. Postprandial insulin production in monkeys was 80-90% normal, so only occasional small insulin supplements were needed.

Ray says these monkeys also have normal liver and kidney function, with no signs of transplant rejection, suggesting that treatment is safe.

“Usually we need to use very aggressive treatments and multiple medications, but in this case we don’t,” he says.

Four monkeys receiving microgel without SA-FasL refused islet transplantation within a few weeks of the procedure.

The goal is to one day provide hospitals with “off-the-shelf-type techniques” that allow surgeons to transplant microgels along with islet transplants, co-authors say. Haval Shirwan At the University of Missouri, I hope that the human exam will begin within two years.

Journal reference: Science Advances, DOI: 10.1126 /sciadv.abm9881

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Diabetes: Protein gels may help treat type 1 diabetes by preventing transplanted pancreatic cells from being rejected

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