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

一种可回收植入物,用于长期封装和维持治疗性异种细胞的存活。

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作者:Suman Bose ,Lisa R Volpatti # ,Devina Thiono # ,Volkan Yesilyurt ,Collin McGladrigan ,Yaoyu Tang ,Amanda Facklam ,Amy Wang ,Siddharth Jhunjhunwala ,Omid Veiseh ,Jennifer Hollister-Lock ,Chandrabali Bhattacharya ,Gordon C Weir ,Dale L Greiner ,Robert Langer ,Daniel G Anderson

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.

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