Stem Cell Reports (Oct 2016)

Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice

  • Susann Rahmig,
  • Romy Kronstein-Wiedemann,
  • Juliane Fohgrub,
  • Nicole Kronstein,
  • Aleksandra Nevmerzhitskaya,
  • Martin Bornhäuser,
  • Max Gassmann,
  • Alexander Platz,
  • Rainer Ordemann,
  • Torsten Tonn,
  • Claudia Waskow

DOI
https://doi.org/10.1016/j.stemcr.2016.08.005
Journal volume & issue
Vol. 7, no. 4
pp. 591 – 601

Abstract

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Human erythro-megakaryopoiesis does not occur in humanized mouse models, preventing the in vivo analysis of human hematopoietic stem cell (HSC) differentiation into these lineages in a surrogate host. Here we show that stably engrafted KIT-deficient NOD/SCID Il2rg−/− KitW41/W41 (NSGW41) mice support much improved human erythropoiesis and platelet formation compared with irradiated NSG recipients. Considerable numbers of human erythroblasts and mature thrombocytes are present in the bone marrow and blood, respectively. Morphology, composition, and enucleation capacity of de novo generated human erythroblasts in NSGW41 mice are comparable with those in human bone marrow. Overexpression of human erythropoietin showed no further improvement in human erythrocyte output, but depletion of macrophages led to the appearance of human erythrocytes in the blood. Human erythropoiesis up to normoblasts and platelet formation is fully supported in NSGW41 mice, allowing the analysis of human HSC differentiation into these lineages, the exploration of certain pathophysiologies, and the evaluation of gene therapeutic approaches.