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

D. An, A. Chiu, J.A. Flanders, W. Song, D. Shou, Y.-C. Lu, L.G. Grunnet, L. Winkel, C. Ingvorsen, N.S. Christophersen, J.J. Fels, F.W. Sand, Y. Ji, L. Qi, Y. Pardo, D. Luo, M. Silberstein, Jintu Fan, M. Ma

Research output: Journal article publicationJournal articleAcademic researchpeer-review

89 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)E263-E272
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number2
DOIs
Publication statusPublished - 9 Jan 2017
Externally publishedYes

Keywords

  • Cell encapsulation
  • Cell transplantation
  • Diabetes
  • Medical device
  • Retrievable

ASJC Scopus subject areas

  • General

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