Human platelets circulating in mice: Applications for interrogating platelet function and survival, the efficacy of antiplatelet therapeutics, and the molecular basis of platelet immunological disorders

Abstract

Herein we describe a novel animal model for examining the survival and function of human platelets following their circulation in non-obese diabetic/severe combined immunodeficient mice. Resting human platelets in platelet-rich plasma are introduced into the retro-orbital plexus, where they are absorbed with high efficiency and circulate for up to 2 days, comprising 10-20% of total circulating platelets. During this period of time, the human platelets can be exposed to a number of biochemical and immunochemical reagents, including novel antithrombotic compounds, or human antiplatelet antibodies that have been implicated in platelet destruction, activation or clearance. Platelets can also be subjected to a variety of storage conditions before infusion, and their relative survival and function following storage and circulation compared. The ability to evaluate in living mice the in vivo function and survival of circulating human platelets may prove valuable for determining mechanisms of antibody-mediated platelet passivation, and aid in the development of novel antiplatelet therapeutics. © 2007 International Society on Thrombosis and Haemostasis.