The hematopoietic stem cells of alpha-thalassemic mice.
The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000528:radiation effects; D003114:Colony-Forming Units Assay; D004912:Erythrocytes / Q000166:cytology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology*; D006454:Hemoglobins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000097:blood* / Q000235:genetics; D010641:Phenotype; D011828:Radiation Chimera; D013154:Spleen / Q000166:cytology; D013789:Thalassemia / Q000097:blood* / Q000235:genetics / Q000473:pathology
D006454:Hemoglobins