Macrophages prevent human red blood cell reconstitution in immunodeficient mice

Z Hu, N Van Rooijen, YG Yang - Blood, The Journal of the …, 2011 - ashpublications.org
Z Hu, N Van Rooijen, YG Yang
Blood, The Journal of the American Society of Hematology, 2011ashpublications.org
An animal model supporting human erythropoiesis will be highly valuable for assessing the
biologic function of human RBCs under physiologic and disease settings, and for evaluating
protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in
NOD/SCID or NOD/SCID/γc−/− mice that were transplanted with human CD34+ fetal liver
cells and fetal thymic tissue. Although a large number of human CD45− CD71+ nucleated
immature erythroid cells were detected in the bone marrow, human RBCs were …
Abstract
An animal model supporting human erythropoiesis will be highly valuable for assessing the biologic function of human RBCs under physiologic and disease settings, and for evaluating protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in NOD/SCID or NOD/SCID/γc−/− mice that were transplanted with human CD34+ fetal liver cells and fetal thymic tissue. Although a large number of human CD45CD71+ nucleated immature erythroid cells were detected in the bone marrow, human RBCs were undetectable in the blood of these mice. Human RBCs became detectable in blood after macrophage depletion but disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin and IL-3 significantly increased human RBC reconstitution in macrophage-depleted, but not control, humanized mice. Significantly more rapid rejection of human RBCs than CD47-deficient mouse RBCs indicates that mechanisms other than insufficient CD47-SIRPα signaling are involved in human RBC xenorejection in mice. All considered, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function.
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