Recovery and Biodistribution ofEx VivoExpanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnullmice

Abstract

Ex vivoexpanded erythroblasts (EBs) may serve as advanced transfusion products provided that lodgment occurs in the macrophage-niche of the marrow permitting maturation. EBs expanded from adult and cord blood expressed the receptors (CXCR4, VLA-4, and P-selectin ligand 1) necessary for interaction with macrophages. However, 4-days following transfusion to intact NOD/SCID/IL2Rγnullmice,CD235aposEBs were observed insideCD235anegsplenic cells suggesting that they underwent phagocytosis. When splenectomized and intact NOD/SCID/IL2Rγnullmice were transfused using retrovirally labeled human EBs, human cells were visualized by bioluminescence imaging only in splenectomized animals. Four days after injection, humanCD235aposcells were detected in marrow and liver of splenectomized mice but only in spleen of controls. HumanCD235aposerythrocytes in blood remained low in all cases. These studies establish splenectomized NOD/SCID/IL2Rγnullmice as a suitable model for tracking and quantification of human EBsin vivo.