Combined liver-cytokine humanization comes to the rescue of circulating human red blood cells.
作者： Emanuela M. Bruscia , Padmavathi Mamillapalli , Toma Tebaldi , Toma Tebaldi , Stephanie Halene
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摘要: 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 liver and cytokine humanization confer enhanced RBC survival the circulation. deleted fumarylacetoacetate hydrolase (Fah) gene MISTRG mice expressing several cytokines place their counterparts. Liver by intrasplenic injection hepatocytes (huHep) eliminated complement C3 reduced Kupffer cell density. Engraftment sickle disease (SCD)–derived hematopoietic stem huHepMISTRGFah−/− resulted vaso-occlusion replicated acute SCD pathology. Combined liver–cytokine–humanized will facilitate study diseases afflicting RBCs, including bone marrow failure, hemoglobinopathies, malaria, also preclinical testing therapies.
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