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iNature's lack of in vivo models of human red blood cell production hinders research on human primary red blood cell (huRBC) diseases (such as sickle cell disease (SCD)) and infectious diseases (such as malaria).
On March 5, 2021, Song Yuanbin and others from Yale University published a research paper titled "Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells" in Science Online.
The research reported on an immunodeficient mouse A model in which the human liver and cytokine humanization are combined to give enhanced human erythropoiesis and RBC survival rates in the circulation.
The study deleted the expression of several human cytokines in place of their murine counterpart fumarylacetoacetate hydrolase (Fah) gene.
Humanization of the liver by injecting human hepatocytes (huHep) into the spleen eliminated murine complement C3 and reduced murine Kupffer cell density.
Implantation of hematopoietic stem cells derived from human sickle cell disease (SCD) into huHepMISTRGFah-/- mice resulted in vascular occlusion, replicating the acute SCD pathology.
Humanized mice combined with hepatocyte cytokines will help to study diseases that plague red blood cells, including bone marrow failure, hemoglobinopathies and malaria, as well as clinical trials before treatment.
Human red blood cells (huRBCs) are one of the most common cell types in the human body.
They are under strict genetic selection throughout human evolution, and their harmful consequences have placed a heavy burden on many populations and healthcare systems.
Species-specific differences in erythropoiesis programs require an in vivo model of human erythropoiesis, but there is no huRBC with continuous maturation in peripheral blood (PB), which can effectively read human functional erythropoiesis and humanization of RBC integrity Immunodeficiency mouse model.
The comprehensive analysis of hematopoietic and RBC diseases such as sickle cell disease (SCD) requires mature RBC in the circulation to be used for disease manifestation and test therapy.
The study reports a mouse model of immunodeficiency in which a combination of human liver and cytokine humanization confers enhanced human erythropoiesis and RBC survival in the circulation.
The study deleted the expression of several human cytokines in place of their murine counterpart fumarylacetoacetate hydrolase (Fah) gene.
Humanization of the liver by injecting human hepatocytes (huHep) into the spleen eliminated murine complement C3 and reduced murine Kupffer cell density.
Implantation of hematopoietic stem cells derived from human sickle cell disease (SCD) into huHepMISTRGFah-/- mice resulted in vascular occlusion, replicating the acute SCD pathology.
Humanized mice combined with hepatocyte cytokines will help to study diseases that plague red blood cells, including bone marrow failure, hemoglobinopathies and malaria, as well as clinical trials before treatment.
In summary, this study introduces the huHepMISTRGFah mouse model with enhanced ability to rebuild human erythropoiesis.
The findings of this study highlight the potential of this model in the research of numerous life-threatening RBC diseases, which involve approximately 5% of the world’s population.
, Including alpha and beta thalassemia and SCD.
In addition, this model may be important in the study of hematopoietic stem cell diseases (such as myelodysplasia).
Erythroleukemia and pathologies that intricately link RBC to the liver, such as malaria.
Therefore, this mouse model may open up other ways for studying the pathophysiological mechanism of the disease and preclinical screening of therapeutic drugs.
Reference message: DOI: 10.
1126/science.
abe2485
On March 5, 2021, Song Yuanbin and others from Yale University published a research paper titled "Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells" in Science Online.
The research reported on an immunodeficient mouse A model in which the human liver and cytokine humanization are combined to give enhanced human erythropoiesis and RBC survival rates in the circulation.
The study deleted the expression of several human cytokines in place of their murine counterpart fumarylacetoacetate hydrolase (Fah) gene.
Humanization of the liver by injecting human hepatocytes (huHep) into the spleen eliminated murine complement C3 and reduced murine Kupffer cell density.
Implantation of hematopoietic stem cells derived from human sickle cell disease (SCD) into huHepMISTRGFah-/- mice resulted in vascular occlusion, replicating the acute SCD pathology.
Humanized mice combined with hepatocyte cytokines will help to study diseases that plague red blood cells, including bone marrow failure, hemoglobinopathies and malaria, as well as clinical trials before treatment.
Human red blood cells (huRBCs) are one of the most common cell types in the human body.
They are under strict genetic selection throughout human evolution, and their harmful consequences have placed a heavy burden on many populations and healthcare systems.
Species-specific differences in erythropoiesis programs require an in vivo model of human erythropoiesis, but there is no huRBC with continuous maturation in peripheral blood (PB), which can effectively read human functional erythropoiesis and humanization of RBC integrity Immunodeficiency mouse model.
The comprehensive analysis of hematopoietic and RBC diseases such as sickle cell disease (SCD) requires mature RBC in the circulation to be used for disease manifestation and test therapy.
The study reports a mouse model of immunodeficiency in which a combination of human liver and cytokine humanization confers enhanced human erythropoiesis and RBC survival in the circulation.
The study deleted the expression of several human cytokines in place of their murine counterpart fumarylacetoacetate hydrolase (Fah) gene.
Humanization of the liver by injecting human hepatocytes (huHep) into the spleen eliminated murine complement C3 and reduced murine Kupffer cell density.
Implantation of hematopoietic stem cells derived from human sickle cell disease (SCD) into huHepMISTRGFah-/- mice resulted in vascular occlusion, replicating the acute SCD pathology.
Humanized mice combined with hepatocyte cytokines will help to study diseases that plague red blood cells, including bone marrow failure, hemoglobinopathies and malaria, as well as clinical trials before treatment.
In summary, this study introduces the huHepMISTRGFah mouse model with enhanced ability to rebuild human erythropoiesis.
The findings of this study highlight the potential of this model in the research of numerous life-threatening RBC diseases, which involve approximately 5% of the world’s population.
, Including alpha and beta thalassemia and SCD.
In addition, this model may be important in the study of hematopoietic stem cell diseases (such as myelodysplasia).
Erythroleukemia and pathologies that intricately link RBC to the liver, such as malaria.
Therefore, this mouse model may open up other ways for studying the pathophysiological mechanism of the disease and preclinical screening of therapeutic drugs.
Reference message: DOI: 10.
1126/science.
abe2485
