| Literature DB >> 33674488 |
Yuanbin Song1,2,3, Liang Shan4,5, Rana Gbyli1,2, Stephanie Halene6,2, Richard A Flavell4,7, Wei Liu1,2, Till Strowig8,9, Amisha Patel1,2, Xiaoying Fu1,2,10, Xiaman Wang1,2,11, Mina L Xu12, Yimeng Gao1,2, Ashley Qin1,2, Emanuela M Bruscia13, Toma Tebaldi1,2,14, Giulia Biancon1,2, Padmavathi Mamillapalli1,2, David Urbonas8, Elizabeth Eynon8, David G Gonzalez15, Jie Chen8, Diane S Krause2,12,16, Jonathan Alderman8.
Abstract
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 huHepMISTRGFah -/- 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.Entities:
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Year: 2021 PMID： 33674488 DOI： 10.1126/science.abe2485
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728