Combined liver-cytokine humanization comes to the rescue of circulating human red blood cells.

Autor:	Song Y; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.; Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China., Shan L; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. liang.shan@wustl.edu stephanie.halene@yale.edu richard.flavell@yale.edu.; Department of Medicine, Pathology and Immunology, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA., Gbyli R; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Liu W; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Strowig T; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.; Helmholtz Centre for Infection Research, Braunschweig, Germany., Patel A; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Fu X; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.; Department of Laboratory Medicine, Shenzhen Children's Hospital, Shenzhen, People's Republic of China., Wang X; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.; Department of Hematology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China., Xu ML; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., Gao Y; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Qin A; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Bruscia EM; Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA., Tebaldi T; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.; Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy., Biancon G; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Mamillapalli P; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Urbonas D; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Eynon E; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Gonzalez DG; Department of Genetics, Yale University School of Medicine, New Haven, CT, USA., Chen J; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Krause DS; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA.; Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.; Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA., Alderman J; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA., Halene S; Section of Hematology, Department of Internal Medicine, Yale Cancer Center, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA. liang.shan@wustl.edu stephanie.halene@yale.edu richard.flavell@yale.edu.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT, USA., Flavell RA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. liang.shan@wustl.edu stephanie.halene@yale.edu richard.flavell@yale.edu.; Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2021 Mar 05; Vol. 371 (6533), pp. 1019-1025.
DOI:	10.1126/science.abe2485
Abstrakt:	In vivo models that recapitulate human erythropoiesis with persistence of circulating red blood cells (RBCs) have remained elusive. We report an immunodeficient murine model in which combined human liver and cytokine humanization confer enhanced human erythropoiesis and RBC survival in the circulation. We deleted the fumarylacetoacetate hydrolase ( Fah ) gene in MISTRG mice expressing several human cytokines in place of their murine counterparts. Liver humanization by intrasplenic injection of human hepatocytes (huHep) eliminated murine complement C3 and reduced murine Kupffer cell density. Engraftment of human sickle cell disease (SCD)-derived hematopoietic stem cells in huHepMISTRG Fah -/- mice resulted in vaso-occlusion that replicated acute SCD pathology. Combined liver-cytokine-humanized mice will facilitate the study of diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, and malaria, and also preclinical testing of therapies. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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