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Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes.

Citation
An, D., et al. “Designing A Retrievable And Scalable Cell Encapsulation Device For Potential Treatment Of Type 1 Diabetes.”. Proceedings Of The National Academy Of Sciences Of The United States Of America, pp. E263-E272.
Center University of Michigan
Author Duo An, Alan Chiu, James A Flanders, Wei Song, Dahua Shou, Yen-Chun Lu, Lars G Grunnet, Louise Winkel, Camilla Ingvorsen, Nicolaj Strøyer Christophersen, Johannes Josef Fels, Fredrik Wolfhagen Sand, Yewei Ji, Ling Qi, Yehudah Pardo, Dan Luo, Meredith Silberstein, Jintu Fan, Minglin Ma
Keywords cell encapsulation, Cell transplantation, diabetes, medical device, retrievable
Abstract

Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.

Year of Publication
2018
Journal
Proceedings of the National Academy of Sciences of the United States of America
Volume
115
Issue
2
Number of Pages
E263-E272
Date Published
12/2018
ISSN Number
1091-6490
DOI
10.1073/pnas.1708806115
Alternate Journal
Proc. Natl. Acad. Sci. U.S.A.
PMID
29279393
PMCID
PMC5777032
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