Cell 'invisibility cloaks' could offer side-effect-free diabetes treatment

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The top row of photos, taken with a scanning electron microscope, shows uncoated cell clusters (islets), with a 50-micrometer, or 0.05 millimeter, scale bar for reference. The bottom row showcases a series of islets covered in a thin film that acts as an "invisibility cloak," hiding the donor cells from the body's immune response and potentially offering researchers a novel approach to treating diabetes. Credit: Kyungsene Lee

Outfitting cells in "invisibility cloaks" may offer an easier, less damaging treatment pathway for people with diabetes undergoing cell therapy, according to researchers at Penn State.

Cell therapy uses specially selected cells to attack infections or jumpstart chemical reactions in the body, such as triggering the production of healthy insulin-producing cells to manage blood sugar levels without requiring a daily injection. However, many existing approaches require patients to continuously take drugs that weaken their immune systems during treatment, which can lead to an increased risk of infection and other serious health issues.

The new approach, published in Nature Biomedical Engineering, involves manufacturing a cell "invisibility cloak" from a jelly-like material known as hydrogel.

The scientists report that this thin layer of hydrogel, called the biomimetic zona pellucida (BZP), effectively hid therapeutic cells from the body's immune system while reducing blood sugar levels in a series of diabetic mice for 100 days, substantially longer than traditional cell therapies for diabetes.

In cell therapy, doctors carefully calibrate donor cells to be introduced into the body's immune system through a process called transplantation, which involves injecting blends of cells and liquid solutions.

Yong Wang, professor of biomedical engineering and corresponding author on the paper, said cell therapies have been approved by the Food and Drug Administration to treat certain diseases, including some cancers. However, cell therapy for treating diabetes is relatively new, with the first treatment approved by the Food and Drug Administration introduced in 2023.

Phase contrast imaging, a specialized type of microscopy, shows uncoated spheroids (left) at three different zoom levels—the top two photos have a 100-micrometer scale bar, while the bottom photo has a 500-micrometer scale bar for reference, or half a millimeter in length. The images of the BZP-coated spheroids (right) illustrate the thin film that surrounds the spheroids, a characteristic that helps protect them from the body's immune response. Credit: Kyungsene Lee

Borrowing a shield from egg cells

"Specific clusters of cells, known as islets, can release sugar-sustaining insulin in the bodies of patients with diabetes," said Wang, who holds an additional affiliation as the Dorothy Foehr Huck and J. Lloyd Huck Chair in Cell Medicine.

"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."

To solve this problem, the team created BZP to mimic a natural coating found on the outside of human egg cells known as the zona pellucida.

Covering donor islets with BZP hides these foreign cells from the body's immune system.

The coating is permeable, meaning that although the cells are protected from the immune system, they can still release therapeutic molecules like insulin into the body, potentially facilitating cell therapy that doesn't require immunosuppressants.

According to Kyungsene Lee, first author on the paper and a postdoctoral researcher at Harvard Medical School who received their doctorate in biomedical engineering from Penn State, although cell encapsulation using hydrogel has been studied for many years, no previous work had recreated the zona pellucida's ultrathin structure and hardening process to form an invisibility cloak for therapeutic cells.

"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," Lee said.

The research is led by corresponding author Yong Wang, professor of biomedical engineering and Dorothy Foehr Huck and J. Lloyd Huck Chair in Cell Medicine at Penn State. Credit: Kate Myers / Penn State

Eight years to thin the coating

The cloak method did not work immediately, Wang explained. It took eight years of consistent development to create a hydrogel layer only 20 micrometers thick—much thinner than a human hair—that could effectively conform to the curved edge of living cells or cell clusters without affecting their functionality.

After ensuring their approach was compatible with living materials, the team coated islets and transplanted them into a group of diabetic mice, monitoring their blood sugar levels over 100 days.

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

The results showed a much longer effective period than uncoated cell therapies, which typically last only one week or less without systemic immunosuppression, Wang said.

Testing how long protection lasts

Going forward, the team plans to further study the BZP approach to better understand the specific duration of resistance each islet transplant could offer. Wang said that in the long term—after more research, refinement and eventually clinical trials—this approach could offer a promising commercial cell therapy platform to treat not just diabetes, but a host of 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," Wang explained. "Simply speaking, BZP could be massively helpful across a broad span of biomedical engineering applications."

Publication details

Biomimetic zona pellucida-encapsulated islets for sustained glycaemic control in immunocompetent mice, Nature Biomedical Engineering (2026). DOI: 10.1038/s41551-026-01775-8

Journal information: Nature Biomedical Engineering

Key medical concepts

Islets of LangerhansImmunosuppressive Agents

Clinical categories

EndocrinologyCommon illnesses & PreventionAllergy and immunology Provided by Pennsylvania State University Who's behind this story?

Sadie Harley

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Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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