Abstract
We have found that the peripheral blood of normal humans contains a significant number of committed erythroid stem cells of high proliferative capacity. These erythroid stem cells closely resemble the murine erythroid burst-forming unit (BFU-E) with respect to proliferative capacity, colony morphology, and erythropoietin requirement. BFU-E were isolated from the peripheral blood of normal individuals by Ficoll-Hypaque density gradient centrifugation and cultured in vitro using the plasma culture technique. Macroscopic erythroid colonies of between 100 and 1000 cells were observed after 10-14 days of culture in the presence of either sheep or human erythropoietin at 0.5-4 units/ml. Individual colonies contained between 3 and 20 subcolonies and reached a maximum mean size of approximately 500 cells. Colony number was linearly related to the cell input, suggesting that a single cellular entity was precursor to each colony. The frequency of cells capable of giving rise to an erythroid colony was at least 100 per ml of blood in a number of individuals tested. The ability to assay significant numbers of erythroid precursor cells of high proliferative capacity from normal peripheral blood should facilitate the study of both normal erythropoiesis and of disease states affecting erythropoiesis in which marrow samples are not available on a routine basis.
Full text
PDF
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Gregory C. J., McCulloch E. A., Till J. E. Erythropoietic progenitors capable of colony formation in culture: state of differentiation. J Cell Physiol. 1973 Jun;81(3):411–420. doi: 10.1002/jcp.1040810313. [DOI] [PubMed] [Google Scholar]
- Heath D. S., Axelrad A. A., McLeod D. L., Shreeve M. M. Separation of the erythropoietin-responsive progenitors BFU-E and CFU-E in mouse bone marrow by unit gravity sedimentation. Blood. 1976 May;47(5):777–792. [PubMed] [Google Scholar]
- Iscove N. N., Sieber F. Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol. 1975 Jan;3(1):32–43. [PubMed] [Google Scholar]
- Iscove N. N., Sieber F., Winterhalter K. H. Erythroid colony formation in cultures of mouse and human bone marrow: analysis of the requirement for erythropoietin by gel filtration and affinity chromatography on agarose-concanavalin A. J Cell Physiol. 1974 Apr;83(2):309–320. doi: 10.1002/jcp.1040830218. [DOI] [PubMed] [Google Scholar]
- McLeod D. L., Shreeve M. M., Axelrad A. A. Improved plasma culture system for production of erythrocytic colonies in vitro: quantitative assay method for CFU-E. Blood. 1974 Oct;44(4):517–534. [PubMed] [Google Scholar]
- Papayannopoulou T. H., Brice M., Stamatoyannopoulos G. Stimulation of fetal hemoglobin synthesis in bone marrow cultures from adult individuals. Proc Natl Acad Sci U S A. 1976 Jun;73(6):2033–2037. doi: 10.1073/pnas.73.6.2033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stephenson J. R., Axelrad A. A., McLeod D. L., Shreeve M. M. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542–1546. doi: 10.1073/pnas.68.7.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tepperman A. D., Curtis J. E., McCulloch E. A. Erythropietic colonies in cultures of human marrow. Blood. 1974 Nov;44(5):659–669. [PubMed] [Google Scholar]