Enhanced Local Immune Suppression: Hope for Beta Cell Replacement Therapies

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Medical devices such as pacemakers and stents that can be implanted in a human body have helped many people lead healthier lives, and researchers are creating such devices for people with type 1 diabetes (T1D) with the hope that the devices can deliver and protect beta cells—the cells that produce insulin in the body—and restore a person to a normal balance of glucose control.

However, biomaterials used to make these devices often trigger an immune response in the body that causes scar tissue to form around the device. This buildup of scar tissue, called fibrosis, can keep the device from working at its full capacity, or even cause it to malfunction entirely.

This problem is a current roadblock when trying to transplant devices with beta cells in them. Fibrosis can keep beta cells from accessing the nutrients and oxygen from the bloodstream that they need to work properly. That’s why a team of researchers, many of them funded by JDRF, have taken the next step toward a solution that enables beta cells to remain functional in the body within encapsulated devices, and without the need for a full-body immune suppression.

In a recent paper the researchers document how they have established a new way to prevent fibrosis from developing around a device. They loaded a crystallized drug into the device that suppresses the immune response in a localized area. Daniel Anderson, Ph.D., an MIT professor and the senior author on the paper, says that the localized delivery of immune suppression is the key development. It focuses the drug’s effect, while not limiting the immune system in other parts of the body. “Systemic delivery of drugs that suppress the immune system, such as the ones used in the Edmonton protocol to prevent graft rejection, can lead to serious side effects.”

Crystallization of the drug produced two benefits. It fits a high density of the drug into a small device, and it enables the drug to be released slowly over a long period of time, because the crystal dissolves at the surface area only, allowing the internal portion to be protected for some time. Currently, the formulation keeps fibrosis at bay for six months and 1.3 years in animal models. The team believes it will be possible to create crystals that last longer by making them larger, or by taking further steps to slow down the rate of deterioration. This result is an improvement on a 2017 study by Anderson and others that showed a drug that blocks the receptors for a specific protein in cells that react to biomaterials can prevent fibrosis by suppressing the immune response in implanted devices.

The crystals themselves may have a wider range of application. “Fibrosis is a fundamental challenge for many implants. We believe the crystals may prove useful in preventing fibrosis in other devices,” said Anderson. Those other devices would include pacemakers, stents, breast implants or sensors.

JDRF-funded investigators that were part of the publication include Joshua C. Doloff, Ph.D., Piotr S. Kowalski, Ph.D., Jose Oberholzer, M.D., Gordon C. Weir, M.D., Dale L. Greiner, Ph.D., Robert Langer, Sc.D., and Daniel G. Anderson, Ph.D.

To learn what JDRF is doing in beta cell replacement research, go here.