A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells

Bose, S and Volpatti, LR and Thiono, D and Yesilyurt, V and McGladrigan, C and Tang, Y and Facklam, A and Wang, AR and Jhunjhunwala, S and Veiseh, O and Hollister-Lock, J and Bhattacharya, C and Weir, GC and Greiner, DL and Langer, R and Anderson, DG (2020) A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells. In: Nature Biomedical Engineering, 4 (8). pp. 814-826.

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Abstract

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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Item Type:	Journal Article
Publication:	Nature Biomedical Engineering
Publisher:	Nature Research
Additional Information:	Copy right for this article belongs to Nature Research
Keywords:	Biocompatibility; Cytology; Mammals; Plastic coatings; Polymeric implants; Pore size; Silicones, Biocompatible devices; Erythropoietin (EPO); Immune suppression; Pancreatic islet; Porous polymeric membrane; Synthetic polymers; Transplanted cells; Xenogeneic cells, Cells
Department/Centre:	Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited:	19 Nov 2020 11:21
Last Modified:	19 Nov 2020 11:21
URI:	http://eprints.iisc.ac.in/id/eprint/65195

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