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

Monique P Gelderman; Chunrong Cheng; Fei Xu; Andrey Skripchenko; Johannah Ryan; Ying Li; Pamela Whitley; Stephen J Wagner; Jaroslav G Vostal

doi:10.1111/trf.15953

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

Transfusion. 2020 Oct;60(10):2379-2388. doi: 10.1111/trf.15953. Epub 2020 Aug 6.

Authors

Monique P Gelderman¹, Chunrong Cheng², Fei Xu¹, Andrey Skripchenko¹, Johannah Ryan¹, Ying Li¹, Pamela Whitley³, Stephen J Wagner⁴, Jaroslav G Vostal¹

Affiliations

¹ Laboratory of Cellular Hematology, Division of Blood Components and Devices, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
² Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
³ Mid-Atlantic Research Facility, American Red Cross, Norfolk, Virginia, USA.
⁴ American Red Cross Holland Laboratory, Rockville, Maryland, USA.

PMID: 32762155
DOI: 10.1111/trf.15953

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.

Publication types

Comparative Study
Research Support, U.S. Gov't, Non-P.H.S.
Validation Study

MeSH terms

Animals
Blood Platelets / metabolism*
Blood Preservation*
Cell Survival
Female
Humans
Male
Mice
Mice, SCID
Platelet Transfusion*
Temperature*
Time Factors

Grants and funding

The animal work was supported by funds from US FDA to JGV and the clinical trial was supported by: U.S Department of Defense (DOD); contract grant number: MIPR10528682; and FDA Medical Countermeasures Initiative (MCMi).