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

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

SUBMITTER: Song Y 

PROVIDER: S-EPMC8292008 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature