Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Sep;82(3):1017–1027. doi: 10.1172/JCI113658

Characterization of a human hematopoietic progenitor cell capable of forming blast cell containing colonies in vitro.

J Brandt 1, N Baird 1, L Lu 1, E Srour 1, R Hoffman 1
PMCID: PMC303616  PMID: 3047166

Abstract

A hematopoietic cell (CFU-B1) capable of producing blast cell containing colonies in vitro was detected using a semisolid culture system. The CFU-B1 has the capacity for self-renewal and commitment to a number of hematopoietic lineages. Monoclonal antibody to the human progenitor cell antigen-1 (HPCA-1) and a monoclonal antibody against the major histocompatibility class II antigen (HLA-DR) were used with fluorescence activated cell sorting to phenotype the CFU-B1. The CFU-B1 was found to express My10 but not HLA-DR antigen; experiments using complement-dependent cytotoxicity to eliminate DR positive cells confirmed this finding. Pretreatment of marrow cells with two chemotherapeutic agents, 5-fluorouracil and 4-hydroperoxycyclophosphamide facilitated detection of CFU-B1 derived colonies, while diminishing or totally inhibiting colony formation by other hematopoietic progenitor cells. CFU-B1-derived colony formation was dependent upon the addition of exogenous hematopoietic growth factors. Media conditioned either by the human bladder carcinoma cell line 5637 or lectin stimulated leukocytes, as well as recombinant granulocyte-macrophage colony stimulating factor, interleukin 3 or interleukin 1 alpha promoted blast cell colony formation. By contrast, neither recombinant erythropoietin, recombinant interleukin 4, purified macrophage colony stimulating factor or recombinant granulocyte colony-stimulating factor alone promoted blast cell colony formation.

Full text

PDF
1017

Images in this article

1020Image
on p.1020
1020Image
on p.1020

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andrews R. G., Singer J. W., Bernstein I. D. Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors. Blood. 1986 Mar;67(3):842–845. [PubMed] [Google Scholar]
  2. Ash R. C., Detrick D. A., Zanjani E. D. Studies of human pluripotential hemopoietic stem cells (CFU-GEMM) in vitro. Blood. 1981 Aug;58(2):309–316. [PubMed] [Google Scholar]
  3. Bagby G. C., Jr, Dinarello C. A., Wallace P., Wagner C., Hefeneider S., McCall E. Interleukin 1 stimulates granulocyte macrophage colony-stimulating activity release by vascular endothelial cells. J Clin Invest. 1986 Nov;78(5):1316–1323. doi: 10.1172/JCI112717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berkow R. L., Straneva J. E., Bruno E., Beyer G. S., Burgess J. S., Hoffman R. Isolation of human megakaryocytes by density centrifugation and counterflow centrigual elutriation. J Lab Clin Med. 1984 May;103(5):811–818. [PubMed] [Google Scholar]
  5. Bodger M. P., Izaguirre C. A., Blacklock H. A., Hoffbrand A. V. Surface antigenic determinants on human pluripotent and unipotent hematopoietic progenitor cells. Blood. 1983 May;61(5):1006–1010. [PubMed] [Google Scholar]
  6. Broudy V. C., Zuckerman K. S., Jetmalani S., Fitchen J. H., Bagby G. C., Jr Monocytes stimulate fibroblastoid bone marrow stromal cells to produce multilineage hematopoietic growth factors. Blood. 1986 Aug;68(2):530–534. [PubMed] [Google Scholar]
  7. Civin C. I., Banquerigo M. L., Strauss L. C., Loken M. R. Antigenic analysis of hematopoiesis. VI. Flow cytometric characterization of My-10-positive progenitor cells in normal human bone marrow. Exp Hematol. 1987 Jan;15(1):10–17. [PubMed] [Google Scholar]
  8. Civin C. I., Strauss L. C., Brovall C., Fackler M. J., Schwartz J. F., Shaper J. H. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol. 1984 Jul;133(1):157–165. [PubMed] [Google Scholar]
  9. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  10. Emerson S. G., Sieff C. A., Wang E. A., Wong G. G., Clark S. C., Nathan D. G. Purification of fetal hematopoietic progenitors and demonstration of recombinant multipotential colony-stimulating activity. J Clin Invest. 1985 Sep;76(3):1286–1290. doi: 10.1172/JCI112087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Falkenburg J. H., Fibbe W. E., Goselink H. M., Van Rood J. J., Jansen J. Human hematopoietic progenitor cells in long-term cultures express HLA-DR antigens and lack HLA-DQ antigens. J Exp Med. 1985 Oct 1;162(4):1359–1369. doi: 10.1084/jem.162.4.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fauser A. A., Messner H. A. Identification of megakaryocytes, macrophages, and eosinophils in colonies of human bone marrow containing neurtophilic granulocytes and erythroblasts. Blood. 1979 May;53(5):1023–1027. [PubMed] [Google Scholar]
  13. Ferrero D., Broxmeyer H. E., Pagliardi G. L., Venuta S., Lange B., Pessano S., Rovera G. Antigenically distinct subpopulations of myeloid progenitor cells (CFU-GM) in human peripheral blood and marrow. Proc Natl Acad Sci U S A. 1983 Jul;80(13):4114–4118. doi: 10.1073/pnas.80.13.4114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fibbe W. E., van Damme J., Billiau A., Voogt P. J., Duinkerken N., Kluck P. M., Falkenburg J. H. Interleukin-1 (22-K factor) induces release of granulocyte-macrophage colony-stimulating activity from human mononuclear phagocytes. Blood. 1986 Dec;68(6):1316–1321. [PubMed] [Google Scholar]
  15. Gordon M. Y., Dowding C. R., Riley G. P., Greaves M. F. Characterisation of stroma-dependent blast colony-forming cells in human marrow. J Cell Physiol. 1987 Jan;130(1):150–156. doi: 10.1002/jcp.1041300121. [DOI] [PubMed] [Google Scholar]
  16. Gordon M. Y., Goldman J. M., Gordon-Smith E. C. 4-Hydroperoxycyclophosphamide inhibits proliferation by human granulocyte-macrophage colony-forming cells (GM-CFC) but spares more primitive progenitor cells. Leuk Res. 1985;9(8):1017–1021. doi: 10.1016/0145-2126(85)90072-4. [DOI] [PubMed] [Google Scholar]
  17. Griffin J. D., Beveridge R. P., Schlossman S. F. Isolation of myeloid progenitor cells from peripheral blood of chronic myelogenous leukemia patients. Blood. 1982 Jul;60(1):30–37. [PubMed] [Google Scholar]
  18. Hodgson G. S., Bradley T. R. Properties of haematopoietic stem cells surviving 5-fluorouracil treatment: evidence for a pre-CFU-S cell? Nature. 1979 Oct 4;281(5730):381–382. doi: 10.1038/281381a0. [DOI] [PubMed] [Google Scholar]
  19. Humphries R. K., Eaves A. C., Eaves C. J. Self-renewal of hemopoietic stem cells during mixed colony formation in vitro. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3629–3633. doi: 10.1073/pnas.78.6.3629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Janossy G., Francis G. E., Capellaro D., Goldstone A. H., Greaves M. F. Cell sorter analysis of leukaemia-associated antigens on human myeloid precursors. Nature. 1978 Nov 9;276(5684):176–178. doi: 10.1038/276176a0. [DOI] [PubMed] [Google Scholar]
  21. Johnson G. R., Metcalf D. Pure and mixed erythroid colony formation in vitro stimulated by spleen conditioned medium with no detectable erythropoietin. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3879–3882. doi: 10.1073/pnas.74.9.3879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Jubinsky P. T., Stanley E. R. Purification of hemopoietin 1: a multilineage hemopoietic growth factor. Proc Natl Acad Sci U S A. 1985 May;82(9):2764–2768. doi: 10.1073/pnas.82.9.2764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kaizer H., Stuart R. K., Brookmeyer R., Beschorner W. E., Braine H. G., Burns W. H., Fuller D. J., Korbling M., Mangan K. F., Saral R. Autologous bone marrow transplantation in acute leukemia: a phase I study of in vitro treatment of marrow with 4-hydroperoxycyclophosphamide to purge tumor cells. Blood. 1985 Jun;65(6):1504–1510. [PubMed] [Google Scholar]
  24. Katz F. E., Tindle R., Sutherland D. R., Greaves M. F. Identification of a membrane glycoprotein associated with haemopoietic progenitor cells. Leuk Res. 1985;9(2):191–198. doi: 10.1016/0145-2126(85)90082-7. [DOI] [PubMed] [Google Scholar]
  25. Keating A., Powell J., Takahashi M., Singer J. W. The generation of human long-term marrow cultures from marrow depleted of Ia (HLA-DR) positive cells. Blood. 1984 Dec;64(6):1159–1162. [PubMed] [Google Scholar]
  26. Keller G. M., Phillips R. A. Detection in vitro of a unique, multipotent hemopoietic progenitor. J Cell Physiol Suppl. 1982;1:31–36. doi: 10.1002/jcp.1041130408. [DOI] [PubMed] [Google Scholar]
  27. Koike K., Ihle J. N., Ogawa M. Declining sensitivity to interleukin 3 of murine multipotential hemopoietic progenitors during their development. Application to a culture system that favors blast cell colony formation. J Clin Invest. 1986 Mar;77(3):894–899. doi: 10.1172/JCI112387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Körbling M., Hess A. D., Tutschka P. J., Kaizer H., Colvin M. O., Santos G. W. 4-hydroperoxycyclophosphamide: a model for eliminating residual human tumour cells and T-lymphocytes from the bone marrow graft. Br J Haematol. 1982 Sep;52(1):89–96. doi: 10.1111/j.1365-2141.1982.tb03864.x. [DOI] [PubMed] [Google Scholar]
  29. Leary A. G., Ogawa M. Blast cell colony assay for umbilical cord blood and adult bone marrow progenitors. Blood. 1987 Mar;69(3):953–956. [PubMed] [Google Scholar]
  30. Lu L., Pelus L. M., Broxmeyer H. E., Moore M. A., Wachter M., Walker D., Platzer E. Enhancement of the proliferation of human marrow erythroid (BFU-E) progenitor cells by prostaglandin E requires the participation of OKT8-positive T lymphocytes and is associated with the density expression of major histocompatibility complex class II antigens on BFU-E. Blood. 1986 Jul;68(1):126–133. [PubMed] [Google Scholar]
  31. Lu L., Walker D., Broxmeyer H. E., Hoffman R., Hu W., Walker E. Characterization of adult human marrow hematopoietic progenitors highly enriched by two-color cell sorting with My10 and major histocompatibility class II monoclonal antibodies. J Immunol. 1987 Sep 15;139(6):1823–1829. [PubMed] [Google Scholar]
  32. Løvhaug D., Pelus L. M., Nordlie E. M., Bøyum A., Moore M. A. Monocyte-conditioned medium and interleukin 1 induce granulocyte-macrophage colony-stimulating factor production in the adherent cell layer of murine bone marrow cultures. Exp Hematol. 1986 Dec;14(11):1037–1042. [PubMed] [Google Scholar]
  33. Metcalf D. The granulocyte-macrophage colony-stimulating factors. Science. 1985 Jul 5;229(4708):16–22. doi: 10.1126/science.2990035. [DOI] [PubMed] [Google Scholar]
  34. Mochizuki D. Y., Eisenman J. R., Conlon P. J., Larsen A. D., Tushinski R. J. Interleukin 1 regulates hematopoietic activity, a role previously ascribed to hemopoietin 1. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5267–5271. doi: 10.1073/pnas.84.15.5267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Moore M. A., Broxmeyer H. E., Sheridan A. P., Meyers P. A., Jacobsen N., Winchester R. J. Continuous human bone marrow culture: Ia antigen characterization of probable pluripotential stem cells. Blood. 1980 Apr;55(4):682–690. [PubMed] [Google Scholar]
  36. Moore M. A., Warren D. J. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7134–7138. doi: 10.1073/pnas.84.20.7134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Morstyn G., Nicola N. A., Metcalf D. Purification of hemopoietic progenitor cells from human marrow using a fucose-binding lectin and cell sorting. Blood. 1980 Nov;56(5):798–805. [PubMed] [Google Scholar]
  38. Nakahata T., Ogawa M. Hemopoietic colony-forming cells in umbilical cord blood with extensive capability to generate mono- and multipotential hemopoietic progenitors. J Clin Invest. 1982 Dec;70(6):1324–1328. doi: 10.1172/JCI110734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nakahata T., Ogawa M. Identification in culture of a class of hemopoietic colony-forming units with extensive capability to self-renew and generate multipotential hemopoietic colonies. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3843–3847. doi: 10.1073/pnas.79.12.3843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Platzer E., Welte K., Gabrilove J. L., Lu L., Harris P., Mertelsmann R., Moore M. A. Biological activities of a human pluripotent hemopoietic colony stimulating factor on normal and leukemic cells. J Exp Med. 1985 Dec 1;162(6):1788–1801. doi: 10.1084/jem.162.6.1788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rennick D., Yang G., Gemmell L., Lee F. Control of hemopoiesis by a bone marrow stromal cell clone: lipopolysaccharide- and interleukin-1-inducible production of colony-stimulating factors. Blood. 1987 Feb;69(2):682–691. [PubMed] [Google Scholar]
  42. Rowley S. D., Colvin O. M., Stuart R. K. Human multilineage progenitor cell sensitivity to 4-hydroperoxycyclophosphamide. Exp Hematol. 1985 May;13(4):295–298. [PubMed] [Google Scholar]
  43. Rowley S. D., Sharkis S. J., Hattenburg C., Sensenbrenner L. L. Culture from human bone marrow of blast progenitor cells with an extensive proliferative capacity. Blood. 1987 Mar;69(3):804–808. [PubMed] [Google Scholar]
  44. Rowley S. D., Zuehlsdorf M., Braine H. G., Colvin O. M., Davis J., Jones R. J., Saral R., Sensenbrenner L. L., Yeager A., Santos G. W. CFU-GM content of bone marrow graft correlates with time to hematologic reconstitution following autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide-purged bone marrow. Blood. 1987 Jul;70(1):271–275. [PubMed] [Google Scholar]
  45. Sieff C. A. Hematopoietic growth factors. J Clin Invest. 1987 Jun;79(6):1549–1557. doi: 10.1172/JCI112988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sieff C. A., Tsai S., Faller D. V. Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor. J Clin Invest. 1987 Jan;79(1):48–51. doi: 10.1172/JCI112806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Siena S., Castro-Malaspina H., Gulati S. C., Lu L., Colvin M. O., Clarkson B. D., O'Reilly R. J., Moore M. A. Effects of in vitro purging with 4-hydroperoxycyclophosphamide on the hematopoietic and microenvironmental elements of human bone marrow. Blood. 1985 Mar;65(3):655–662. [PubMed] [Google Scholar]
  48. Stanley E. R., Bartocci A., Patinkin D., Rosendaal M., Bradley T. R. Regulation of very primitive, multipotent, hemopoietic cells by hemopoietin-1. Cell. 1986 Jun 6;45(5):667–674. doi: 10.1016/0092-8674(86)90781-6. [DOI] [PubMed] [Google Scholar]
  49. Van Zant G. Studies of hematopoietic stem cells spared by 5-fluorouracil. J Exp Med. 1984 Mar 1;159(3):679–690. doi: 10.1084/jem.159.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Visser J. W., Bauman J. G., Mulder A. H., Eliason J. F., de Leeuw A. M. Isolation of murine pluripotent hemopoietic stem cells. J Exp Med. 1984 Jun 1;159(6):1576–1590. doi: 10.1084/jem.159.6.1576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Williams D. E., Straneva J. E., Shen R. N., Broxmeyer H. E. Purification of murine bone-marrow-derived granulocyte-macrophage colony-forming cells. Exp Hematol. 1987 Mar;15(3):243–250. [PubMed] [Google Scholar]
  52. Winchester R. J., Ross G. D., Jarowski C. I., Wang C. Y., Halper J., Broxmeyer H. E. Expression of Ia-like antigen molecules on human granulocytes during early phases of differentiation. Proc Natl Acad Sci U S A. 1977 Sep;74(9):4012–4016. doi: 10.1073/pnas.74.9.4012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Winton E. F., Colenda K. W. Use of long-term human marrow cultures to demonstrate progenitor cell precursors in marrow treated with 4-hydroperoxycyclophosphamide. Exp Hematol. 1987 Jul;15(6):710–714. [PubMed] [Google Scholar]
  54. Zucali J. R., Dinarello C. A., Oblon D. J., Gross M. A., Anderson L., Weiner R. S. Interleukin 1 stimulates fibroblasts to produce granulocyte-macrophage colony-stimulating activity and prostaglandin E2. J Clin Invest. 1986 Jun;77(6):1857–1863. doi: 10.1172/JCI112512. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES