PMID: 42904Nov 1, 1979

Prevention of genetic anemias in mice by microinjection of normal hematopoietic stem cells into the fetal placenta

Proceedings of the National Academy of Sciences of the United States of America
R A Fleischman, B Mintz

Abstract

Mice homozygous for mutant genes at the W locus have a marked macrocytic anemia that is fatal in some genotypes. The defect is believed to originate in the developmentally pluripotent hematopoietic stem cell population. Anemia is first grossly manifest on day 13 of gestation, when the liver is the chief hematopoietic organ. The known paucity of blood-forming foci in livers of homozygotes and the limited formation of their erythrocytes suggested that such fetuses-unlike normal ones-might have conditions favorable for in utero seeding of genetically normal hematopoietic tissue. If this were accomplished before day 13, the anemia might essentially be prevented, or at least substantially mitigated, and normalcy soon achieved by cell selection. This proved to be the case. Allogeneic normal fetal liver cells were microinjected into the blood vessels of the fetal placenta on day 11 of gestation. Of eight mutant homozygotes born from segregating matings, six (four W/W, two W(v)/W(v)) were successfully populated with donor cells. Strain-specific hemoglobin markers demonstrated replacement of the erythroid lineage with the normal type, the rate of substitution being more rapid in the W/W (ordinarily more anemic) recipients. Strain-specif...Continue Reading

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Jun 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·B MintzR P Custer
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Related Concepts

Microinjections
Pluripotent Stem Cells
Placenta Specimen
Lymphocytes as Percentage of Blood Leukocytes (Lab Test)
Uterus
Neoplasm of Uncertain or Unknown Behavior of Thymus
Blood Vessel
White Blood Cell Count Procedure
Placenta
Disease of Thymus Gland

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