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A retrievable implant for the long-term encapsulation and survival of therapeutic xenogeneic cells.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2020-03-30 , DOI: 10.1038/s41551-020-0538-5
Suman Bose 1 , Lisa R Volpatti 1, 2 , Devina Thiono 1, 3 , Volkan Yesilyurt 1, 3 , Collin McGladrigan 1, 3 , Yaoyu Tang 1, 3 , Amanda Facklam 1 , Amy Wang 2 , Siddharth Jhunjhunwala 1, 4 , Omid Veiseh 1, 5 , Jennifer Hollister-Lock 6 , Chandrabali Bhattacharya 1 , Gordon C Weir 6 , Dale L Greiner 7 , Robert Langer 1, 2, 3, 8 , Daniel G Anderson 1, 2, 3, 8
Affiliation  

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.



中文翻译:

一种可回收的植入物,用于治疗性异种细胞的长期封装和存活。

移植的治疗细胞的长期功能通常需要全身免疫抑制。在这里,我们显示了一种可回收的植入物,其包含有机硅储层和多孔聚合物膜,可在免疫功能小鼠的腹膜腔内植入植入物后保护封装在其中的人类细胞。孔径为1 µm的膜允许宿主巨噬细胞迁移到装置中,而不会损失移植的细胞,而孔径<0.8 µm的膜则阻止了它们被免疫细胞浸润。合成聚合物涂层可防止纤维化,对于设备的长期功能而言是必不可少的。在超过130天的时间里,该设备一直支持能够在免疫功能正常的小鼠中分泌促红细胞生成素的人类细胞,以及携带可诱导促红细胞生成素分泌的诱导基因回路的转基因人类细胞。来自封装在该装置中并植入糖尿病小鼠的大鼠的胰岛在超过75天的时间内恢复了小鼠的血糖正常值。这种生物相容性装置为在没有免疫抑制的情况下移植工程细胞提供了可回收的解决方案。

更新日期:2020-04-24
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