Improved Human Erythropoiesis and Platelet Formation in Humanized NSGW41 Mice.
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.
Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Susann
S
Rahmig
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, 01307 Dresden, Germany; Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, 01307 Dresden, Germany.
Romy
R
Kronstein-Wiedemann
Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Juliane
J
Fohgrub
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, 01307 Dresden, Germany; Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, 01307 Dresden, Germany.
Nicole
N
Kronstein
Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany.
Aleksandra
A
Nevmerzhitskaya
Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, 01307 Dresden, Germany.
Martin
M
Bornhäuser
Institute of Veterinary Physiology, Vetsuisse Faculty and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
Max
M
Gassmann
DKMS Cord Blood Bank, Enderstrasse 94, 01277 Dresden, Germany.
Alexander
A
Platz
Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, 01307 Dresden, Germany.
Rainer
R
Ordemann
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, 01307 Dresden, Germany; Universitätsklinikum Carl Gustav Carus der TU Dresden, Medizinische Klinik und Poliklinik I, 01307 Dresden, Germany.
Torsten
T
Tonn
Regeneration in Hematopoiesis and Animal Models in Hematopoiesis, Institute for Immunology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Electronic address: claudia.waskow@tu-dresden.de.
Claudia
C
Waskow
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D036101:Cord Blood Stem Cell Transplantation; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics*; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics; D034061:Thrombopoiesis / Q000235:genetics*
D053631:Interleukin Receptor Common gamma Subunit; D004921:Erythropoietin; D019009:Proto-Oncogene Proteins c-kit