STOMACH IMPLANT FOR LONG-TERM ERYTHROPOIETIN EXPRESSION IN RATS

To approach the goal of consistent long-term erythropoietin (Epo) expr ession in vivo, we developed an implantation procedure in which transd uced autologous vascular smooth muscle was introduced into rats in a c hamber created from a polytetrafluoroethylene (PTFE) ring placed under the serosa of the stomach. The implant became vascularized and permit ted the long-term survival of smooth muscle cells expressing Epa. Hema tocrits of treated animals increased rapidly and monitored over 12 mon ths gave a mean value of 56.0 +/- 4.0% (P <.001; n = 9), increased fro m a presurgery mean of 42.3 +/- 1.6%, Hemoglobin levels rose from a pr esurgery mean of 15.2 +/- 0.4 g/dL and far 12 months were significantl y elevated with a mean value of 19.5 +/- 1.3 g/dL (P <.001; n = 9). Th e hematocrit: and hemoglobin levels of control animals receiving human adenosine deaminase (ADA)-expressing cells were not significantly dif ferent from baseline (P >.05; n = 5). In response to tissue oxygenatio n, kidney, and (to a lesser extent) liver are specific organs that syn thesize Epo, Treated animals showed downregulation of endogenous Epo m RNA in kidney over a 12-month period. The PTFE implant provides sustai ned gene delivery, is safe, and is minimally invasive. It allows easy engraftment of transduced cells and may be applied generally to the sy stemic delivery of therapeutic proteins such as hormones and clotting factors. (C) 1998 by The American Society of Hematology.