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 system during treatment, which can lead to increased risk of infection among other serious health issues.

The new approach, published today (Aug 14) in Nature Biomedical Engineering, involves manufacturing a cell "invisibility cloak" out of a jelly-like material known as hydrogel. The scientists reported that this thin layer of hydrogel, called the biomimetic zona pellucida (BZP), effectively hid the 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 that 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.

"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 postdoc 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."

Kyungsene Lee, first author on the paper and postdoc at Harvard Medical School

The cloak method did not work immediately, Wang explained. It took eight years of consistent development to develop a hydrogel layer only 20 micrometers thick - much thinner than a human hair - that could effectively lay against the curved edge of living cells or cell clusters without impacting 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 to 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 stayed diabetes free for over 100 days without continuously needing immunosuppressants. The results showcased a much longer effective period than uncoated cell therapies, which typically last only one week or even shorter without systemic immunosuppression, Wang said. 

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."

Other authors currently affiliated with Penn State include Xiaojun "Lance" Lian, associate professor of biology and of biomedical engineering; Yuguo Lei, associate professor of biomedical engineering and faculty director of the Sartorius Cell Culture Facility in the Huck Institutes of the Life Sciences; Hong Zheng, professor of medicine and of molecular precision medicine at the Penn State College of Medicine; Yixun Wang, Alexander L. Mark, Chein-Wei Wu, Ana Aviles Vargas, Yuhong Jian and Thomas I. McDougal, who are currently biomedical engineering graduate students at Penn State; and Selina Y. Lin, a biomedical engineering undergraduate student.

Additional co-authors include Jennifer Z. Wang, a high school researcher at the time of the work who is now is an undergraduate student at Duke; and Xuelin Wang, Connie Wen, Brandon Davis and James Coyne, who all earned their doctorates from Penn State.

Source:

Journal reference:

Lee, K., et al. (2026). Biomimetic zona pellucida-encapsulated islets for sustained glycaemic control in immunocompetent mice. Nature Biomedical Engineering. DOI: 10.1038/s41551-026-01775-8. https://www.nature.com/articles/s41551-026-01775-8