A genetically engineered, nonthrombogenic cellular lining for LVADs: In vitro preconditioning before in vivo implantation

Because of the clinical success of left ventricular assist devices (LVADs) used for short-term "bridge to transplant" and the limited availability of donor organs, heart assist devices are being considered for long-term impla ntation as an alternative to heart transplantation. In an effort to improve biocompatibility, our laboratory has developed a nonthrombogenic cellular lining from genetically engineered smooth muscle cells (CE-SMC) for the The rmocardiosystems Heartmate LVAD. Smooth muscle cells have been transduced w ith the gene for endothelial nitric oxide synthase (NOS ill) and produce NO at concentrations thai. reduce platelet deposition and smooth muscle fell proliferation when tested in vitro. In this investigation, the adhesive cap abilities of GE-SMC linings were examined. An in vitro circulatory loop was designed to expose cell lined LVADs to in vivo operating conditions. Cumul ative cell loss from cell lined LVADs was less than 10% after 24 hours of f low. Using a protocol for "preconditioning" the cell lining within the mock circulatory loop, the first implantation of an LVAD containing a genetical ly engineered SMC lining was successfully implemented in a bovine model. Re sults from this 24 hour study indicate that the flow-conditioned cellular l ining remained intact with no evidence of thromboembolization and only mini mal changes in coagulation studies.