Validation of a SCID mouse model for transfusion by concurrent comparison of circulation kinetics of human platelets, stored under various temperature conditions, between human volunteers and mice. Issue 10 (6th August 2020)

• Record Type: Journal Article
• Authors: Gelderman, Monique P.; Cheng, Chunrong; Xu, Fei; Skripchenko, Andrey; Ryan, Johannah; Li, Ying; Whitley, Pamela; Wagner, Stephen J.; Vostal, Jaroslav G.
• Is Part Of: Transfusion. Volume 60:Issue 10(2020)
• Page Start: 2379
• Page End: 2388
• Publication Date: 2020-08-06
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.15953
• Languages: English
• ISSNs: 0041-1132

Abstract

Abstract: Background: Initial evaluation of new platelet (PLT) products for transfusion includes a clinical study to determine in vivo recovery and survival of autologous radiolabeled PLTs in healthy volunteers. These studies are expensive and do not always produce the desired results. A validated animal model of human PLTs in vivo survival and recovery used pre‐clinically could reduce the risk of failing to advance product development. Study Design and Methods: An immunodeficient (SCID) mouse model to evaluate recovery of human PLTs was compared to a radiolabeling study in human volunteers. Autologous apheresis PLTs stored for 7 days at room temperature (RT), thermo‐cycled (TC), and cold temperature (CT) were radiolabeled and infused into healthy humans (n = 16). The same PLTs, non‐radiolabeled, were also infused into mice (n = 160) on the same day. Blood samples from humans and mice were collected to generate clearance curves of PLTs in circulation. Flow cytometry was used to detect human PLTs in mouse blood. Results: Human and mouse PLTs were cleared with one phase exponential clearance. Relative differences for initial recovery and AUC, expressed as ratio of test and control PLTs, were similar in humans and mice. The initial recovery ratio of TC/RT was 0.73 ± 0.07 in humans and 0.67 ± 0.14 in mice. The ratio for CT/TC was 0.53 ± 0.06 in humans and 0.75 ± 0.18 in mice. Conclusion: The SCID mouse model can provide information on relative differences of initial in vivo recovery and AUC between control and alternatively stored/processed human PLTs that is predictive of performance in healthy human volunteers.