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Combined liver–cytokine humanization comes to the rescue of circulating human red blood cells
- Source :
- Science
- Publication Year :
- 2021
- Publisher :
- American Association for the Advancement of Science (AAAS), 2021.
-
Abstract
- A red-letter day for RBC research The study of primary human red blood cell (huRBC) disorders such as sickle cell disease (SCD) and infectious diseases such as malaria has been hampered by a lack of in vivo models of human erythropoiesis. Song et al. transferred human fetal liver cells into MISTRG mice, which are immunodeficient and are genetically engineered with several human genes involved in hematopoiesis. This approach was unsuccessful because mature huRBCs are rapidly destroyed in the mouse liver. They then used CRISPR-Cas9 to mutate these mice into a fumarylacetoacetate hydrolase–deficient strain, allowing them to replace the mouse liver with engrafted human hepatocytes. These mice exhibited enhanced human erythropoiesis and circulating huRBC survival and could recapitulate SCD pathology when reconstituted with SCD-derived HSCs. Science , this issue p. 1019
- Subjects :
- Erythrocytes
Hydrolases
medicine.medical_treatment
Cell
Anemia, Sickle Cell
Article
Mice
medicine
Animals
Humans
Erythropoiesis
Multidisciplinary
business.industry
Kupffer cell
Bone marrow failure
Middle Aged
Hematopoietic Stem Cells
medicine.disease
Mice, Mutant Strains
Disease Models, Animal
Haematopoiesis
medicine.anatomical_structure
Cytokine
Liver
Blood Circulation
Immunology
Cytokines
Fumarylacetoacetate hydrolase
Female
Stem cell
business
Gene Deletion
Subjects
Details
- ISSN :
- 10959203 and 00368075
- Volume :
- 371
- Database :
- OpenAIRE
- Journal :
- Science
- Accession number :
- edsair.doi.dedup.....00c36851149b99920bc74c7f10c9803f