Long-term generation of colony-forming cells in liquid culture of CD34+ cord blood cells in the presence of recombinant human stem cell factor.

Human cord blood was used as a source of progenitor and stem cells to evaluate the effect of recombinant human stem-cell factor (SCF) on colony formation and the generation of colony-forming cells (CFC) under highly defined, serum-deprived conditions. SCF interacted with a number of hematopoietic growth factors to stimulate colony growth and was particularly effective in stimulating the formation of mixed-cell colonies from CD34+ soybean agglutinin negative (SBA-) cells. In suspension culture of CD34+, SBA- cells, SCF alone was unable to maintain cell numbers or CFC but, in combination with interleukin-3 (IL-3), increased input numbers of cells by 10-fold and increased CFC of all kinds by nearly 20-fold. This included erythroid burst-forming cells (BFU-E), granulocyte/macrophage (GM) CFC, and mixed-cell CFC. In contrast, CD34- SBA- cells neither gave rise to CFC nor were maintained by combinations of growth factors including SCF. SCF interacted with erythropoietin (Epo) and granulocyte colony-stimulating factor (G-CSF) to maintain large numbers of cells as well as to generate a twofold to threefold increase in CFC in the case of Epo, and a 10-fold increase in CFC in the case of G-CSF. With Epo, the predominant CFC generated were BFU-E and erythroid CFC and many of the cells in suspension were erythroblasts. In contrast, SCF plus G-CSF resulted in large numbers of granulocytes at various stages of maturation and the CFC generated were almost exclusively granulocytic-CFC. IL-1 and IL-6, alone or in combination with SCF, showed little or no ability to increase cell numbers or generate CFC. In summary, SCF interacts with a variety of hematopoietic growth factors to promote colony formation, particularly mixed-cell colony formation, and also, in suspension culture, SCF interacts with IL-3, G-CSF, and Epo to generate large numbers of differentiated cells as well as a variety of CFC for up to 1 month.

[1]  K. Zsebo,et al.  Human burst-forming units-erythroid need direct interaction with stem cell factor for further development. , 1991, Blood.

[2]  D. Williams,et al.  Mast cell growth factor (c-kit ligand) supports the growth of human multipotential progenitor cells with a high replating potential. , 1991, Blood.

[3]  J. Adamson,et al.  Effects of recombinant human stem cell factor (SCF) on the growth of human progenitor cells in vitro , 1991, Journal of cellular physiology.

[4]  K. Zsebo,et al.  The effects on hematopoiesis of recombinant stem cell factor (ligand for c-kit) administered in vivo to mice either alone or in combination with granulocyte colony-stimulating factor. , 1991, Blood.

[5]  J. Adamson,et al.  Stem cell factor induces proliferation and differentiation of highly enriched murine hematopoietic cells. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[6]  I. Bernstein,et al.  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. , 1991, Blood.

[7]  D. Williams,et al.  Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. , 1991, Blood.

[8]  K. Zsebo,et al.  Recombinant human stem cell factor synergises with GM-CSF, G-CSF, IL-3 and epo to stimulate human progenitor cells of the myeloid and erythroid lineages. , 1991, Experimental hematology.

[9]  D. Williams,et al.  Influence of murine mast cell growth factor (c-kit ligand) on colony formation by mouse marrow hematopoietic progenitor cells. , 1991, Experimental hematology.

[10]  B. Hogan,et al.  Embryonic expression of a haematopoietic growth factor encoded by the SI locus and the ligand for c-kit , 1990, Nature.

[11]  C. March,et al.  Identification of a ligand for the c-kit proto-oncogene , 1990, Cell.

[12]  David A. Williams,et al.  Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor , 1990, Cell.

[13]  K. Zsebo,et al.  Primary structure and functional expression of rat and human stem cell factor DNAs , 1990, Cell.

[14]  P. Leder,et al.  The kit ligand: A cell surface molecule altered in steel mutant fibroblasts , 1990, Cell.

[15]  J. Adamson,et al.  The biology of hematopoietic growth factors: studies in vitro under serum-deprived conditions. , 1990, Experimental hematology.

[16]  K. Nocka,et al.  Candidate ligand for the c‐kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. , 1990, The EMBO journal.

[17]  N. Iscove,et al.  Precursors (pre-CFCmulti) of multilineage hemopoietic colony-forming cells quantitated in vitro. Uniqueness of IL-1 requirement, partial separation from pluripotential colony-forming cells, and correlation with long term reconstituting cells in vivo. , 1990, Journal of immunology.

[18]  J. Kurtzberg,et al.  Hematopoietic reconstitution in a patient with Fanconi's anemia by means of umbilical-cord blood from an HLA-identical sibling. , 1989, The New England journal of medicine.

[19]  H. Broxmeyer,et al.  Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[20]  C. Caux,et al.  Combined and sequential effects of human IL-3 and GM-CSF on the proliferation of CD34+ hematopoietic cells from cord blood. , 1989, Blood.

[21]  J. Adamson,et al.  Effect of recombinant hematopoietic growth factors on proliferation of human marrow progenitor cells in serum-deprived liquid culture. , 1988, Blood.

[22]  J. Adamson,et al.  In vitro differentiation of human granulocyte/macrophage and erythroid progenitors: comparative analysis of the influence of recombinant human erythropoietin, G-CSF, GM-CSF, and IL-3 in serum-supplemented and serum-deprived cultures. , 1988, Blood.

[23]  J. Ihle,et al.  Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[24]  A. Migliaccio,et al.  Early Hemopoietic Differentiation: The Action of Multi‐CSF Is Complemented by Lineage Specific Growth Factors , 1987, Annals of the New York Academy of Sciences.

[25]  A. Migliaccio,et al.  Cloning of human erythroid progenitors (BFU‐E) in the absence of fetal bovine serum , 1987, British journal of haematology.

[26]  Yu-Chung Yang,et al.  Human IL-3 (multi-CSF): Identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3 , 1986, Cell.

[27]  J. Adamson,et al.  Genomic cloning, characterization, and multilineage growth-promoting activity of human granulocyte-macrophage colony-stimulating factor. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Gabrilove,et al.  Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. , 1986, Science.

[29]  E. Russell,et al.  Developmental studies of mouse hereditary anemias. , 1984, American journal of medical genetics.

[30]  R. Good,et al.  Enrichment for CFU-C from murine and human bone marrow using soybean agglutinin. , 1982, Blood.

[31]  P. Sarvella,et al.  STEEL, A NEW DOMINANT GENE IN THE HOUSE MOUSEWith Effects on Coat Pigment and Blood , 1956 .

[32]  J. Adamson,et al.  In vitro differentiation and proliferation of human hematopoietic progenitors: the effects of interleukins 1 and 6 are indirectly mediated by production of granulocyte-macrophage colony-stimulating factor and interleukin 3. , 1991, Experimental hematology.

[33]  J. Kurtzberg,et al.  Umbilical cord blood hematopoietic stem and repopulating cells in human clinical transplantation. , 1991, Blood cells.

[34]  I. Bernstein,et al.  Recombinant human stem cell factor, a c-kit ligand, stimulates hematopoiesis in primates. , 1991, Blood.

[35]  E. Russell.  Hereditary anemias of the mouse: a review for geneticists. , 1979, Advances in genetics.