Waldman, Joshua P.Vogel, ThomasBurlak, ChristopherCoussios, ConstantinDominguez, JavierFriend, PeterRees, Michael A.2015-09-152015-09-152013-07Waldman, J. P., Vogel, T., Burlak, C., Coussios, C., Dominguez, J., Friend, P., & Rees, M. A. (2013). Blocking porcine sialoadhesin improves extracorporeal porcine liver xenoperfusion with human blood. Xenotransplantation, 20(4), 239–251. http://doi.org/10.1111/xen.12043https://hdl.handle.net/1805/6921BACKGROUND: Patients in fulminant hepatic failure currently do not have a temporary means of support while awaiting liver transplantation. A potential therapeutic approach for such patients is the use of extracorporeal perfusion with porcine livers as a form of "liver dialysis". During a 72-h extracorporeal perfusion of porcine livers with human blood, porcine Kupffer cells bind to and phagocytose human red blood cells (hRBC) causing the hematocrit to decrease to 2.5% of the original value. Our laboratory has identified porcine sialoadhesin expressed on Kupffer cells as the lectin responsible for binding N-acetylneuraminic acid on the surface of the hRBC. We evaluated whether blocking porcine sialoadhesin prevents the recognition and subsequent destruction of hRBCs seen during extracorporeal porcine liver xenoperfusion. METHODS: Ex vivo studies were performed using wild type pig livers perfused with isolated hRBCs for 72-h in the presence of an anti-porcine sialoadhesin antibody or isotype control. RESULTS: The addition of an anti-porcine sialoadhesin antibody to an extracorporeal porcine liver xenoperfusion model reduces the loss of hRBC over a 72-h period. Sustained liver function was demonstrated throughout the perfusion. CONCLUSIONS: This study illustrates the role of sialoadhesin in mediating the destruction of hRBCs in an extracorporeal porcine liver xenoperfusion model.en-USPublisher PolicyAcute liver failureAdhesion moleculesHepatic failureKupffer cellsLiver assist -- supportLiver failureLiver support devicesMacrophagesXenograft rejectionXenoperfusionXenotransplantationArticle