In vivo recovery of human platelets in severe combined immunodeficient mice as a measure of platelet damage

Abstract

Clinical performance of human platelet (PLT) products processed or stored under novel conditions is difficult to predict based on in vitro studies alone. Recovery and survival of radiolabeled PLTs in human subjects are used as surrogate markers for PLT efficacy in development of new products. Such experiments pose some risk to the participants, can be a financial burden on the sponsor, and may stifle innovation and development of new PLT products. Animal models for in vivo recovery and survival of human PLTs are limited by rapid, immune-mediated clearance of human cells. The severe combined immunodeficient (SCID) mice allowed prolonged circulation of human PLTs and were used to detect differences in recovery and survival between chemically damaged, aged PLTs, or normal PLTs. Human PLTs were transfused into SCID and wild-type (WT) mice, and the recoveries and survival times were detected in mouse whole blood by flow cytometry with an anti-human CD41-fluorescein isothiocyanate monoclonal antibody. Recoveries of damaged PLTs were compared to normal PLTs. Recoveries were significantly shorter in WT than in SCID mice at 4 hours after transfusion (WT, 20.8 +/- 5.4%, n = 12; SCID, 63.8 +/- 8.4%, n = 10) and with a t((1/2)) estimate of 2 hours for WT and 7 hours for SCID mice. Human PLTs damaged either by chemical treatment or by improper storage exhibited decreased recoveries in SCID mice. The SCID mouse model can detect differences between damaged and control human PLTs and could be useful in evaluating novel PLT collection, processing, and storage technologies that may impact PLT quality.