| Literature DB >> 29279393 |
Duo An1, Alan Chiu1, James A Flanders2, Wei Song1, Dahua Shou3, Yen-Chun Lu1, Lars G Grunnet4, Louise Winkel4, Camilla Ingvorsen4, Nicolaj Strøyer Christophersen4, Johannes Josef Fels5, Fredrik Wolfhagen Sand4, Yewei Ji6, Ling Qi6, Yehudah Pardo7, Dan Luo1,8,9, Meredith Silberstein10, Jintu Fan3, Minglin Ma11.
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, Ca2+-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.Entities:
Keywords: cell encapsulation; cell transplantation; diabetes; medical device; retrievable
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Year: 2017 PMID: 29279393 PMCID: PMC5777032 DOI: 10.1073/pnas.1708806115
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN: 0027-8424 Impact factor: 11.205