A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells
Name
nihms-1563572.pdf
Description
Accepted version
Size
2.18 MB
Format
Adobe PDF
Checksum (MD5)
f0c2a0f89fa52c3c48002253b067fd4d
Author(s)
Bose, Suman
Volpatti, Lisa R
Thiono, Devina
Yesilyurt, Volkan
McGladrigan, Collin
Tang, Yaoyu
Facklam, Amanda
Wang, Amy
Jhunjhunwala, Siddharth
Veiseh, Omid
Date Issued
2020
Journal
Nature Biomedical Engineering
Publisher
Springer Science and Business Media LLC
Version
Author's final manuscript
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. The long-term function of transplanted therapeutic cells typically requires systemic immune suppression. Here, we show that a retrievable implant comprising a silicone reservoir and a porous polymeric membrane protects human cells encapsulated in it after implant transplantation in the intraperitoneal space of immunocompetent mice. Membranes with pores 1 µm in diameter allowed host macrophages to migrate into the device without the loss of transplanted cells, whereas membranes with pore sizes <0.8 µm prevented their infiltration by immune cells. A synthetic polymer coating prevented fibrosis and was necessary for the long-term function of the device. For >130 days, the device supported human cells engineered to secrete erythropoietin in immunocompetent mice, as well as transgenic human cells carrying an inducible gene circuit for the on-demand secretion of erythropoietin. Pancreatic islets from rats encapsulated in the device and implanted in diabetic mice restored normoglycaemia in the mice for over 75 days. The biocompatible device provides a retrievable solution for the transplantation of engineered cells in the absence of immunosuppression.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
10.1038/S41551-020-0538-5
https://doi.org/10.1038/S41551-020-0538-5
