Researchers Develop Invisible Cell Armor for Safer Diabetes Treatment

According to Pennsylvania State University researchers, outfitting cells in “invisibility cloaks” may provide a simpler, less harmful treatment strategy for people with diabetes undergoing cell therapy.

Without the need for regular injections, cell therapy uses carefully chosen cells to fight infections or trigger chemical processes in the body, such as generating healthy cells that produce insulin to control blood sugar levels.

However, many of the current methods require patients to take drugs that impair their immune systems continuously while undergoing therapy, which might raise their risk of infection and other major health problems.

The new method, published in Nature Biomedical Engineering, involves creating a cell "invisibility cloak" from hydrogel, a jelly-like substance. The biomimetic zona pellucida (BZP), a thin layer of hydrogel, successfully concealed the therapeutic cells from the body's immune system while lowering blood sugar levels in a group of diabetic mice for 100 days - much longer than conventional cell therapies for diabetes, according to the researchers.

In cell therapy, doctors carefully prepare donor cells before introducing them into the body's immune system through transplantation, which can include infusing cell and liquid mixtures.

According to Yong Wang, a professor of biomedical engineering and the study's corresponding author, the US Food and Drug Administration (FDA) has approved cell treatments to treat particular diseases, including several cancers. However, cell therapy for diabetes is still in its early stages, with the first FDA-approved treatment launched in 2023.

Specific clusters of cells, known as islets, can release sugar-sustaining insulin in the bodies of patients with diabetes. However, these donor islets are targeted and attacked by the patient’s immune system. Existing treatment options require patients to continuously take immunosuppressants to stop this response, which can lead to significant side effects, including cancer.

Yong Wang, Study Corresponding Author and Professor, Biomedical Engineering, Pennsylvania State University

To address this issue, the scientists developed BZP to replicate a natural coating present on the exterior of human egg cells called the zona pellucida. Covering donor islets with BZP conceals these foreign cells from the body’s immune system. The coating is permeable, meaning that even though the cells are protected from the immune system, they may still release therapeutic molecules such as insulin into the body, potentially enabling cell therapy without immunosuppressants.

Although cell encapsulation using hydrogel has been studied for many years, no prior work had replicated the zona pellucida's ultrathin structure and hardening process to create an invisibility cloak for therapeutic cells, according to Kyungsene Lee, the study’s first author and a postdoc at Harvard Medical School who earned their doctorate in biomedical engineering from Penn State.

Our body is amazing – by mimicking the natural, ultrathin coating formed by proteins on egg cells, we can fortify and cloak cells for therapeutic transplantation.

Kyungsene Lee, Study First Author and Postdoctoral Researcher, Harvard Medical School

Wang noted that the cloak approach did not function instantly. It required eight years of persistent work to create a hydrogel layer barely 20 micrometers thick – considerably thinner than a human hair – that could efficiently adhere to the curved edges of living cells or cell clusters without impairing their activity.

After showing the method was compatible with live materials, the researchers coated islets and transplanted them into diabetic mice, monitoring blood sugar levels for 100 days.

Compared to untreated diabetic mice and mice treated with uncoated islets, mice treated with BZP-coated islets had their blood sugar levels restored to normal within a week, and the majority of those mice remained diabetes-free for more than 100 days without the need for immunosuppressants.

The findings revealed a significantly longer effective time than uncoated cell treatments, which normally last about one week or less without systemic immunosuppression, according to Wang.

The team intends to do more research on the BZP technique to better understand the precise period of resistance that each islet transplant may provide. Wang believes that, in the long run, with additional study, refinement, and eventually clinical trials, this strategy could become a commercial cell therapy platform to treat not only diabetes but a variety of other diseases and conditions across the body.

This technique could be useful in immunotherapy, priming cells to resist chronic disease, or in regenerative medicine, stimulating cell growth to regenerate tissues in damaged or lost organs. Simply speaking, BZP could be massively helpful across a broad span of biomedical engineering applications.

Yong Wang, Study Corresponding Author and Professor, Biomedical Engineering, Pennsylvania State University