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First immune-evading cells created to treat type 1 diabetes

According to researchers, most type 1 diabetics are children and teenagers. This is a disease that is historically hard to manage with drugs. @Shutterstock

A device-free transplantation of insulin-producing cells may help scientists find a cure to type 1 diabetes. Read on to know more.

Written by Jahnavi Sarma |Published : August 21, 2020 10:44 AM IST

Type 1 diabetes is a lifelong condition that is challenging to manage, even with automated devices that deliver insulin to regulate blood sugar. Transplants of pancreatic beta islets, clusters of cells that make insulin and other hormones from donor tissue, can provide a cure but require patients to take life-long immunosuppressing drugs, which carry serious risks. For decades, researchers have sought a better way to replenish lost pancreatic cells. Now, thanks to a new study, a device-free transplantation of insulin-producing cells may help scientists find a cure to the disease.

Salk Institute scientists have made a major advance in the pursuit of a safe and effective treatment for type 1 diabetes, an illness that impacts an estimated 1.6 million Americans with a cost of $14.4 billion annually. Using stem cell technology, Salk researchers generated the first human insulin-producing pancreatic cell clusters able to evade the immune system. These "immune shielded" cell clusters controlled blood glucose without immunosuppressive drugs once transplanted in the body. The journal Nature published this study.

Regenerative medicine for type 1 diabetes

According to researchers, most type 1 diabetics are children and teenagers. This is a disease that is historically hard to manage with drugs. Regenerative medicine in combination with immune shielding may make a real difference in the field by replacing damaged cells with lab-generated human islet-like cell clusters that produce normal amounts of insulin on demand.

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In an earlier study too stem-cell-derived beta-like cells that produced insulin was developed. But these were not functional. The cells did not release insulin in response to glucose, as they were simply under powered. But researcher discovered a genetic switch called ERR-gamma that, when flipped, "turbo-charges" the cells. When ERR-gamma is added, the cells have the energy they need to do their job. These cells are healthy and robust and can deliver insulin when they sense high glucose levels.

Tissue transplant may be the key to treat type 1 diabetes

A critical part of the new study was to develop a way to grow beta-like cells in a three-dimensional environment that approximates the human pancreas. This gave the cells an islet-like property. Importantly, the team discovered that a protein called WNT4 was able to turn on the ERR-gamma-driven maturation switch. This combination of steps generated functional cell clusters that mimic human islets: so-called human islet-like organoids (HILOs).

Protecting the transplanted cells from the immune system

Researchers also tackled the complex issue of immune rejection. Normal tissue transplants require lifelong immune suppressive therapies to protect the tissue from being attacked by the immune system. But these therapies also increase the risk for infections. Inspired by the successes of immunotherapy drugs for cancer, researchers initially showed that the checkpoint protein PD-L1 protected the transplanted cells.

By expressing PD-L1, which acts as an immune blocker, the transplanted organoids are able to hide from the immune system. A method to induce PD-L1 in HILOs with short pulses of the protein interferon gamma was then developed. When transplanted into diabetic mice, these immune-evasive HILOs provided sustained blood glucose control in diabetic mice with healthy immune systems. According to researchers, you can protect HILOs from the immune system without genetic manipulation. If this is developed as a therapy, patients will not need to take immune-suppressing drugs. However, they agree that further research needs to be undertaken to arrive at any definite conclusion.

(With inputs from Agencies)

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