According to researchers at the University of Pennsylvania, cloaking cells in “invisibility cloaks” could offer a simpler and less harmful treatment path for people with diabetes undergoing cell therapy.
Cell therapy employs specially selected cells to fight infections or trigger chemical reactions within the body—such as stimulating the production of healthy, insulin-producing cells to manage blood sugar levels—thereby eliminating the need for daily injections. However, many current approaches require patients to take immunosuppressive drugs throughout treatment, which can lead to an increased risk of infection and other serious health issues.
A new approach, published in the journal Nature Biomedical Engineering, involves creating a cellular “invisibility cloak” from a jelly-like material known as hydrogel. Scientists reported that this thin hydrogel layer—termed the biomimetic zona pellucida (BZP)—effectively shielded therapeutic cells from the body’s immune system. Simultaneously, it successfully lowered blood sugar levels in diabetic mice for 100 days, a duration significantly longer than that achieved by traditional cell therapies for diabetes.
In cell therapy, doctors carefully calibrate donor cells for introduction into the body’s immune system via a process known as transplantation, which involves administering mixtures of cells and liquid solutions. Yong Wang, a professor of biomedical engineering and the study’s corresponding author, noted that cell therapies have been approved by the FDA for treating specific conditions, including certain types of cancer. However, cell therapy for diabetes is a relatively new field; the first such treatment received FDA approval in 2023. “Certain cell clusters, known as islets, can secrete insulin to help manage blood sugar levels in patients with diabetes,” said Wang, who also holds the Dorothy Foehr Huck and J. Lloyd Huck Chair in Cellular Medicine. “However, these donor islets are attacked by the patient’s immune system. Current treatment options require the continuous use of immunosuppressants to halt this reaction, which can lead to serious side effects, including cancer.”
To address this issue, the team created BZP, a material that mimics the natural coating found on the exterior of human egg cells, known as the zona pellucida. Coating donor islets with BZP hides these foreign cells from the body’s immune system. The coating is permeable; while the cells are shielded from the immune system, they can still release therapeutic molecules—such as insulin—into the body, potentially enabling cell therapies that do not require immunosuppressants.
According to Kyung-Sun Lee, the study’s lead author and a postdoctoral researcher at Harvard Medical School (who earned his PhD in biomedical engineering at Penn State), while hydrogel-based cell encapsulation has been studied for years, no previous work had successfully replicated the ultrathin structure and hardening process of the zona pellucida to create an “invisibility cloak” for therapeutic cells.
The “cloak” method did not work immediately, Wang explained. It took eight years of sustained development to create a hydrogel layer just 20 micrometers thick—far thinner than a human hair—that could effectively coat the curved surfaces of living cells or clusters without impairing their function. After confirming that their approach was compatible with living materials, the team coated the islets and transplanted them into a group of diabetic mice, monitoring blood sugar levels for 100 days.
Compared to untreated diabetic mice and those treated with uncoated islets, the mice receiving BZP-coated islets saw their blood sugar levels return to normal within a week—and most remained diabetes-free for over 100 days without the need for continuous immunosuppressant therapy. The results demonstrated a much longer period of efficacy than uncoated cell therapies, which typically last only a week or less without systemic immunosuppression, Wang noted.
Moving forward, the team plans to further investigate the BZP approach to better understand the specific duration of resistance that each islet transplant can provide. Wang noted that in the long term—following further research, refinement, and eventually clinical trials—this approach could become a promising commercial platform for treating not only diabetes but also a wide range of diseases and conditions throughout the body.
“This method could be useful in immunotherapy, preparing cells to withstand chronic diseases, or in regenerative medicine, by stimulating cell growth to regenerate tissue in damaged or lost organs,” Wang explained. “Simply put, BZP could be extremely val…
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