Abstract
To directly study the biological properties of purified hematopoietic colony-forming cell precursors, cells with a CD34+ CD45RAlo CD71lo phenotype were purified from human bone marrow using density separation and fluorescence-activated cell sorting, and were cultured in serum-free culture medium supplemented with various cytokines. In the presence of interleukin 3 (IL-3), IL-6, erythropoietin, and mast cell growth factor (a c-kit ligand), cell numbers increased approximately 10(6)-fold over a period of 4 wk, and the percentage of cells that expressed transferrin receptors (CD71) increased from less than 0.1% at day 0 to greater than 99% at day 14. Interestingly, the absolute number of CD34+ CD71lo cells did not change during culture. When CD34+ CD71lo cells were sorted from expanded cultures and recultured, extensive cell production was repeated, again without significant changes in the absolute number of cells with the CD34+ CD71lo phenotype that were used to initiate the (sub)cultures. These results document that primitive hematopoietic cells can generate progeny without an apparent decrease in the size of a precursor cell pool.
MeSH Terms
Antigens, CD/analysis,metabolism
Antigens, CD34
Bone Marrow Cells
Cell Separation/methods
Cell Survival/drug effects
Cells, Cultured
Centrifugation, Density Gradient/methods
Colony-Forming Units Assay
Culture Media, Serum-Free
Cytokines/pharmacology
DNA Replication/drug effects
Erythropoiesis/drug effects,physiology
Erythropoietin/pharmacology
Flow Cytometry/methods
Hematopoietic Cell Growth Factors/pharmacology
Hematopoietic Stem Cells/cytology,drug effects
Humans
Interleukin-3/pharmacology
Interleukin-6/pharmacology
Phenotype
Receptors, Transferrin/drug effects,metabolism
Stem Cell Factor
Thymidine/metabolism
Chemicals
Antigens, CD
Antigens, CD34
Culture Media, Serum-Free
Cytokines
Hematopoietic Cell Growth Factors
Interleukin-3
Interleukin-6
Receptors, Transferrin
Stem Cell Factor
Erythropoietin
Thymidine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lansdorp P M
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Dragowska W
References (29)
29 references, click to expand
-
Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium.
Cell. 1990 Oct 5;63(1):195-201
PMID: 2208278
-
Review: Stratton Lecture 1990. Clinical implications of positive and negative hematopoietic stem cell regulators.
Blood. 1991 Jul 1;78(1):1-19
PMID: 2070044
-
Cyanine dye labeling reagents--carboxymethylindocyanine succinimidyl esters.
Cytometry. 1990;11(3):418-30
PMID: 2340776
-
Construction and use of a safe and efficient amphotropic packaging cell line.
Virology. 1988 Dec;167(2):400-6
PMID: 2462307
-
Precursors of colony-forming cells in humans can be distinguished from colony-forming cells by expression of the CD33 and CD34 antigens and light scatter properties.
J Exp Med. 1989 May 1;169(5):1721-31
PMID: 2469766
-
Characterization and partial purification of human marrow cells capable of initiating long-term hematopoiesis in vitro.
Blood. 1989 Oct;74(5):1563-70
PMID: 2790186
-
Human liquid bone marrow culture in serum-free medium.
Br J Haematol. 1989 Oct;73(2):143-7
PMID: 2818936
-
Cellular interactions.
Blood. 1988 Aug;72(2):373-85
PMID: 3042038
-
Monoclonal antibodies specific for the M- and N-forms of human glycophorin A.
Mol Immunol. 1983 Dec;20(12):1353-62
PMID: 6197636
-
Ubiquitous cell-surface glycoprotein on tumor cells is proliferation-associated receptor for transferrin.
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4515-9
PMID: 6270680
-
Complete replacement of serum in primary cultures of erythropoietin-dependent red cell precursors (CFU-E) by albumin, transferrin, iron, unsaturated fatty acid, lecithin and cholesterol.
Exp Cell Res. 1980 Mar;126(1):121-6
PMID: 7358084
-
The segregation of DNA in epithelial stem cells.
Cell. 1978 Nov;15(3):899-906
PMID: 728994
-
Cytokine-dependent long-term culture of highly enriched precursors of hematopoietic progenitor cells from human bone marrow.
J Clin Invest. 1990 Sep;86(3):932-41
PMID: 1697607
-
Differential and synergistic effects of human granulocyte-macrophage colony-stimulating factor and human granulocyte colony-stimulating factor on hematopoiesis in human long-term marrow cultures.
Blood. 1991 Feb 1;77(3):493-9
PMID: 1703795
-
The effect of recombinant mast cell growth factor on purified murine hematopoietic stem cells.
J Exp Med. 1991 May 1;173(5):1205-11
PMID: 1708810
-
Culture of phenotypically defined hematopoietic stem cells and other progenitors at limiting dilution on Dexter monolayers.
Blood. 1991 Aug 15;78(4):945-52
PMID: 1678290
-
Selective expression of CD45 isoforms on functional subpopulations of CD34+ hemopoietic cells from human bone marrow.
J Exp Med. 1990 Jul 1;172(1):363-6
PMID: 1694223
-
Identification of a ligand for the c-kit proto-oncogene.
Cell. 1990 Oct 5;63(1):167-74
PMID: 1698553
-
The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus.
Cell. 1990 Oct 5;63(1):225-33
PMID: 1698557
-
Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells.
Blood. 1991 Mar 15;77(6):1218-27
PMID: 1705833
-
Separation of functionally distinct subpopulations of primitive human hematopoietic cells using rhodamine-123.
Exp Hematol. 1991 Jun;19(5):338-42
PMID: 1709107
-
Recombinant human stem cell factor enhances the formation of colonies by CD34+ and CD34+lin- cells, and the generation of colony-forming cell progeny from CD34+lin- cells cultured with interleukin-3, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor.
Blood. 1991 Jun 1;77(11):2316-21
PMID: 1710148
-
Mechanisms that regulate the cell cycle status of very primitive hematopoietic cells in long-term human marrow cultures. II. Analysis of positive and negative regulators produced by stromal cells within the adherent layer.
Blood. 1991 Jul 1;78(1):110-7
PMID: 1712638
-
Expression of CD34 on human B cell precursors.
Clin Exp Immunol. 1991 Jul;85(1):168-73
PMID: 1712682
-
CD45 cell surface antigens are linked to stimulation of early human myeloid progenitor cells by interleukin 3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), a GM-CSF/IL-3 fusion protein, and mast cell growth factor (a c-kit ligand).
J Exp Med. 1991 Aug 1;174(2):447-58
PMID: 1713254
-
Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells.
Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7420-4
PMID: 1714603
-
Single laser three color immunofluorescence staining procedures based on energy transfer between phycoerythrin and cyanine 5.
Cytometry. 1991;12(8):723-30
PMID: 1794253
-
Enhanced hematopoietic activity of a human granulocyte/macrophage colony-stimulating factor-interleukin 3 fusion protein.
Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5809-13
PMID: 1829529
-
Functional characterization of individual human hematopoietic stem cells cultured at limiting dilution on supportive marrow stromal layers.
Proc Natl Acad Sci U S A. 1990 May;87(9):3584-8
PMID: 2333304