A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells.
Nat Biomed Eng
; 4(8): 814-826, 2020 08.
Article
em En
| MEDLINE
| ID: mdl-32231313
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Próteses e Implantes
/
Transplante de Células
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Sobrevivência de Enxerto
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biomed Eng
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos