Researchers believe that the novel approach offers major advantages over traditional encapsulation strategies
Scientists at the Diabetes Research Institute (DRI) in Miami together with collaborators at the Ècole Polytechnique Fèdèrale de Lausanne (EPFL) in Switzerland have developed a new cell encapsulation method with the goal of protecting transplanted insulin-producing islet cells from destruction by the immune system. Their novel process for conformal coating of islets (similar to applying a tight-fitting “shrink wrap” around the cells) with thin, complete and uniform capsules of similar thickness, has been designed to specifically address what are considered to be the limitations of traditional cell encapsulation methods. The results of their recent study, which demonstrates that their unique conformal coatings allows efficient encapsulation of islets without compromising viability and function of the cells, were recently published in the prestigious journal Proceedings of the National Academy of Sciences.
The encapsulation of islet cells has been researched extensively as a potential therapy for type 1 diabetes. However, there has been limited success in translating this approach to patients due to a number of issues, including the size of the capsules themselves, the materials used to coat the cells, and the inability to transplant encapsulated islets in sites that favor oxygen and nutrient support to the transplanted cells to keep them healthy and functioning long term. The new process developed by the research team overcomes these critical challenges.
“Previous efforts in islet encapsulation have failed partly because of the large size of conventional capsules,” said Alice Tomei, Ph.D., assistant professor of surgery and cell transplantation at the DRI, principal investigator and lead author of the published paper. “Islets vary considerably in size and shape, and production of traditional capsules is standardized to accommodate the largest size. This results in capsules that are too large for the smaller islets. The extra space inside the capsule delays access to oxygen and nutrients, causing many islets to die. It also delays the islet’s main function — sensing blood glucose and releasing the right amount of insulin in real time to avoid hyper- and hypoglycemia. Finally, such a large islet size does not allow implantation in sites that are more islet-friendly, and within devices that have been designed to house the islets in the manner that is most favorable for their function, like the BioHub.”
In the study, Dr. Tomei and her team observed that the conformal-coated islets exhibited no delay in glucose-stimulated insulin release and there was no loss of function when the cells were placed in culture prior to transplantation, which is often observed with non-coated, or naked, islets. When transplanted into experimental syngeneic models of type 1 diabetes, the conformal-coated islets restored normal glucose levels and maintained those levels for more than 100 days with no apparent signs of chronic site reactivity to the implanted capsule material.
In addition, because the conformal-coated cells do not take up the same amount of space as the conventional larger capsules, researchers will be able to implant these coated cells within a confined site, like a DRI BioHub mini-organ.
The research began several years ago, when Dr. Tomei was working at the Institute of Bioengineering at the EPFL in Switzerland in the laboratory of Jeffrey A. Hubbell, Ph.D., the article’s senior author. She came to the DRI in 2010, bringing the research with her.
“Pancreatic islets are the most sensitive cells that I have worked with, and keeping them functional while enclosing them in a protective bubble has proved to be very challenging,” said Tomei. The scientists will continue to optimize their unique cell encapsulation process with the goal of translating this research to people living with diabetes.
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Funding for the research was provided by the Diabetes Research Institute Foundation, JDRF-Helmsley, Children with Diabetes Foundation, the National Institutes of Health (NIH), BioRep Technologies, and Converge Biotech.
Lori Weintraub, APR