losartan-potassium and Foreign-Body-Reaction

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.

Topics: Animals; Capsules; Cell Transplantation; Coated Materials, Biocompatible; Diabetes Mellitus, Experimental; Equipment Design; Erythropoietin; Foreign-Body Reaction; Graft Survival; HEK293 Cells; Humans; Islets of Langerhans; Islets of Langerhans Transplantation; Mice; Permeability; Prostheses and Implants; Rats; Transplantation, Heterologous