A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells
| Autor: | Siddharth Jhunjhunwala, Volkan Yesilyurt, Omid Veiseh, Chandrabali Bhattacharya, Amanda L. Facklam, Daniel G. Anderson, Robert Langer, Gordon C. Weir, Lisa R. Volpatti, Suman Bose, Amy Wang, Yaoyu Tang, Dale L. Greiner, Collin McGladrigan, Devina Thiono, Jennifer Hollister-Lock |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell Transplantation medicine.medical_treatment Transgene Transplantation Heterologous Islets of Langerhans Transplantation Biomedical Engineering Medicine (miscellaneous) Capsules Bioengineering Article Permeability Diabetes Mellitus Experimental Islets of Langerhans Mice 03 medical and health sciences 0302 clinical medicine Immune system Coated Materials Biocompatible medicine Animals Humans Secretion Erythropoietin Chemistry Foreign-Body Reaction Pancreatic islets Graft Survival HEK 293 cells Immunosuppression Equipment Design Prostheses and Implants Rats Computer Science Applications Cell biology Transplantation HEK293 Cells 030104 developmental biology medicine.anatomical_structure Implant 030217 neurology & neurosurgery Biotechnology Stem Cell Transplantation |
| Zdroj: | Nature biomedical engineering |
| ISSN: | 2157-846X |
| Popis: | 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 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. A retrievable, porous and anti-fibrotic macrodevice for the encapsulation of cells provides long-term protection to human cells expressing therapeutic proteins after device implantation in the intraperitoneal space of immunocompetent mice. |
| Databáze: | OpenAIRE |
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