Skip to main content
Log in

Kinetic models of hemopoietic stem cell populations

  • Part I Hemopoietic Precursors
  • Published:
In Vitro Aims and scope Submit manuscript

Summary

Recent techniques enabled a series of quantitative studies to be made with various aspects of the stem cell functions. Results from several laboratories appear to agree on certain main points: the existence of a pluripotential stem cell in the small rodent, capable of forming visible colonies of hemopoietic foci in the spleen and the existence of some undifferentiated but committed precursor cells from which the differentiating and maturing cell populations originate. There is evidence that the primary stem cell is in a low turnover state in the normal animal, although on demand it is capable of fast and prolonged proliferative activity. The committed undifferentiated precursor cells differ greatly, depending on which cell line they represent. Some of these are in high turnover state in the normal animal (e.g., erythropoietin-responsive cells), others do not appear to be capable of proliferation (e.g., focus forming cells). Perturbation of the steady states by irradiation of the animal, or by treatment with cytotoxic drugs results in recovery patterns which yield valuable kinetic information.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Osgood, E. E. 1957. A unifying concept of the etiology of the leukemias, lymphomas and cancers. J. Nat. Cancer Inst.18: 155–166.

    PubMed  CAS  Google Scholar 

  2. Osgood, E. E. 1959. Blood cell survival in tissue cultures. Ann. N. Y. Acad. Sci.77: 777–796.

    Article  PubMed  CAS  Google Scholar 

  3. Lajtha, L. G., Oliver, R. and Gurney, C. W. 1962. Kinetic model of a bone-marrow stem-cell population. Brit. J. Haemat.8: 442–460.

    PubMed  CAS  Google Scholar 

  4. Lajtha, L. G. 1963. On the concept of the cell cycle. J. Cell. Comp. Physiol. (Suppl. 1), p. 143–145.

    Google Scholar 

  5. Gilbert, C. W. and Lajtha, L. G. 1964. The importance of cell population kinetics in determining response to irradiation of normal and malignant tissue, p. 474–497.In:Cellular Radiation Biology: XVIIIth Annual Symposium on Fundamental Cancer Research, Texas, 1964. The Williams & Wilkins company, Baltimore.

    Google Scholar 

  6. Newton, C. M. 1966. Modeling the stemcell system—current status. Ann. N. Y. Acad. Sci.128: 781–789.

    Article  PubMed  CAS  Google Scholar 

  7. Kretchmar, A. L. 1965. A model of hemopoiesis for mammalian recovery experiments, p. 41–46. Oak Ridge Institute of Nuclear Studies Research Report ORINS-53.

  8. Okunewick, J. P. and Kretchmar, A. L. 1967. A mathematical model for post-irradiation hematopoietic recovery. RAND Corporation Research Memorandum RM-5272-PR.

  9. Kretchmar, A. L. 1966. Erythropoietin: Hypothesis of action tested by analog computer. Science152: 367–370.

    Article  CAS  Google Scholar 

  10. Gurney, C. W., Wackman, N. and Filmanowicz, E. 1961. Studies on erythropoiesis. XVII. Some quantitative aspects of the erythropoietic response to erythropoietin. Blood17: 531–546.

    PubMed  CAS  Google Scholar 

  11. Schooley, J. C. 1965. Responsiveness of hematopoietic tissue to erythropoietin in relation to the time of administration and duration of action of the hormone. Blood25: 795–808.

    PubMed  CAS  Google Scholar 

  12. Till, J. E., McCulloch, E. A. and Siminovitch, L. 1964. A stochastic model of stem cell proliferation based on the growth of spleen colony-forming cells. Proc. Nat. Acad. Sci.51: 29–36.

    Article  PubMed  CAS  Google Scholar 

  13. Bruce, W. R. and McCulloch, E. A. 1964. The effect of erythropoietic stimulation on the hemopoietic colony-forming cells of mice. Blood23: 216–232.

    PubMed  CAS  Google Scholar 

  14. Till, J. E. and McCulloch, E. A. 1961. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat. Res.14: 213–222.

    Article  PubMed  CAS  Google Scholar 

  15. Becker, A. J., McCulloch, E. A. and Till, J. E. 1963. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature (London)197: 452–454.

    Article  CAS  Google Scholar 

  16. Gurney, C. W., Hofstra, D. and Mangalik, A. 1965. Physiological studies of primitive hemopoietic cells, p. 21. Paper presented at an International Symposium on grafting isologous hemopoietic cells, Paris, 1964.In: O. Jacobson and M. Doyle (eds.) Argonne Cancer Research Hospital Seminannual Report to the Atomic Energy Commission.

  17. Hanna, I. R. A. 1967. Response of early erythroid precursors to bleeding. Nature (London)214: 355–357.

    Article  CAS  Google Scholar 

  18. Lajtha, L. G., Schoefield, R. and Pozzi, L. V. Cell Tiss. Kinct. (In press).

  19. Hodgson, G. 1967. Effect of vinblastine and 4-amino-N10 methyl pteroyl-glutamic acid on the erythropoietin responsive cell. Proc. Soc. Exp. Biol. Med.125: 1206–1209.

    PubMed  CAS  Google Scholar 

  20. Valeriote, F. A., Bruce, W. R. and Meeker, B. E. 1966. Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony-forming cells of mice to vinblastine administeredin vivo. J. Nat. Cancer Inst.36: 21–27.

    PubMed  CAS  Google Scholar 

  21. Bruce, W. R., Meeker, B. E. and Valeriote, F. A. 1966. Comparison of the sensitivity of normal hematopoietic and transplanted lymphoma colony-forming cells to chemotherapeutic agents administeredin vivo. J. Nat. Cancer Inst.37: 233–245.

    PubMed  CAS  Google Scholar 

  22. Becker, A. H., McCulloch, E. A., Siminovitch, L. and Till, J. E. 1965. The effect of differing demands for blood cell production on DNA synthesis by hemopoietic colony-forming cells of mice. Blood26: 296–308.

    PubMed  CAS  Google Scholar 

  23. Pluznik, D. H. and Sachs, L. 1965. The cloning of normal mast cells in tissue culture. J. Cell. Comp. Physiol.66: 319–324.

    Article  CAS  Google Scholar 

  24. Pluznik, D. H. and Sachs, L. 1966. The induction of clones of normal “mast” cells by a substance from conditioned medium. Exp. Cell Res.43: 553–563.

    Article  PubMed  CAS  Google Scholar 

  25. Bradley, T. R. and Metcalf, D. 1966. The growth of mouse bone marrow cellsin vitro. Austral. J. Exp. Biol. Med. Sci.44: 287–300.

    CAS  Google Scholar 

  26. Bradley, T. R., Metcalf, D. and Robinson, W. 1967. Stimulation by leukaemic sera of colony formation in solid agar cultures by proliferation of mouse bone marrow cells. Nature (London)213: 926–927.

    Article  CAS  Google Scholar 

  27. Fox, M. (To be published.)

  28. Bradley, T. R., Robinson, W. and Metcalf, D. 1967. Colony productionin vitro by normal polycythaemic and anaemic bone marrow. Nature (London)214: 511.

    Article  CAS  Google Scholar 

  29. Porteous, D. D. and Lajtha, L. G. 1966. On stem-cell recovery after irradiation. Brit. J. Haemat.12: 177–187.

    PubMed  CAS  Google Scholar 

  30. McCulloch, E. A. and Till, J. E. 1962. The sensitivity of cells from normal mouse bone marrow to gamma irradiationin vitro andin vivo. Radiat. Res.16: 822–832.

    Article  PubMed  CAS  Google Scholar 

  31. Russell, E. S., Bernstein, S. E., McFarland, E. C. and Modeen, W. R. 1963. The cellular basis of differential radiosensitivity of normal and genetically anemic mice. Radiat. Res.20: 677–694.

    Article  PubMed  CAS  Google Scholar 

  32. Keighley, G., Russell, E. S. and Lowy, P. H. 1962. Response of normal and genetically anaemic mice to erythropoietic stimuli. Brit. J. Haemat.8: 429–441.

    PubMed  CAS  Google Scholar 

  33. McCulloch, E. A., Siminovitch, L. and Till, J. E. 1964. Spleen-colony formation in anemic mice of genotype WWv. Science144: 844–846.

    Article  PubMed  CAS  Google Scholar 

  34. Steeves, R. A., Bennett, M., Mirand, E. A. and Cudkowicz, G. 1968. Genetic control by the W locus of susceptibility to (Friend) spleen focus-forming virus. Nature (London)218: 372–374.

    Article  CAS  Google Scholar 

  35. Blackett, N. M., Roylance, P. J. and Adams, K. 1964. Studies of the capacity of bone-marrow cells to restore erythropoiesis in heavily irradiated rats. Brit. J. Haemat.10: 453–467.

    PubMed  CAS  Google Scholar 

  36. Blackett, N. M. 1967. Erythropoiesis in the rat under continuous γ-irradiation at 45 rads/day. Brit. J. Haemat.13: 915–923.

    PubMed  CAS  Google Scholar 

  37. Barnes, D. W. H., Ford, C. E. and Loutit, J. R. 1959. Gresses en sèrie moelle osseuse homologue chez des souris irradièes. Sang30: 762–765.

    PubMed  CAS  Google Scholar 

  38. Van Bekkum, D. W. and Weyzen, W. W. H. 1961. Serial transfer of isologous and homologous hematopoietic cells in irradiated hosts. Path. Biol.9: 888–893.

    Google Scholar 

  39. Barnes, D. W. H., Loutit, J. R. and Micklem, H. S. 1962. ‘Secondary disease’ of radiation chimeras: A syndrome due to lymphoid aplasia. Ann. N. Y. Acad. Sci.99: 374–385.

    Article  PubMed  CAS  Google Scholar 

  40. Koller, P. C. and Doak, S. M. A. 1963. Serial transplantation of haemopoietic tissue in irradiated hosts, p. 59–64.In R. J. C. Harris (ed.)Cellular Basis and Aetiology of Late Somatic Effects of Ionizing Radiation. Academic Press Inc., New York.

    Google Scholar 

  41. Cudkowicz, G., Upton, A. C., Shearer, G. M. and Hughes, W. L. 1964. Lymphocyte content and proliferative capacity of serially transplanted mouse bone marrow. Nature (London)201: 165–167.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lajtha, L.G. Kinetic models of hemopoietic stem cell populations. In Vitro 4, 14–21 (1969). https://doi.org/10.1007/BF02618207

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02618207

Keywords

Navigation