Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Identification and characterization of an inhibitor of haemopoietic stem cell proliferation

Nature volume 344, pages 442–444 (1990)Cite this article

Abstract

THE haemopoietic system has three main compartments: multi-potential stem cells, intermediate stage progenitor cells and mature cells. The availability of simple reproducible culture systems1 has made possible the characterization and purification of regulators of the progenitor cells, including colony-stimulating factors and interleukins. In contrast, our knowledge of the regulators involved in the control of stem cell proliferation is limited. The steady-state quiescent status of the haemopoietic stem cell compartment is thought to be controlled by locally acting regulatory elements present in the stromal microenvironment2, but their purification has been hampered by the lack of suitable culture systems. We have recently developed a novel in vitro colony assay that detects a primitive cell (CPU-A) 3 which has similar proliferative charac-teristics, in normal and regenerating bone marrow, to the CFU-S (haemopoietic stem cells, as defined by the spleen colony assay4) and which responds to CFU-S-specific proliferation regulators. We have now used this assay to purify to homogeneity a macrophage-derived reversible inhibitor of haemopoietic stem cell proliferation (stem cell inhibitor, SCI). Antibody inhibition and sequence data indicate that SCI is identical to a previously described cytokine, macrophage inflammatory protein-lα ( MIP-lα), and that SCI/MIP-lα is functionally and antigenically iden-tical to the CFU-S inhibitory activity obtained from primary cultures of normal bone marrow cells5. The biological activities of SCI/MIP-lα suggest that it is a primary negative regulator of stem cell proliferation and that it has important therapeutic appli-cations in protecting haemopoietic stem cells from damage during cytotoxic therapies for cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Metcalf, D. Molecular Control of Blood Cells (Harvard University Press, 1988).

    Google Scholar 

  2. Toksoz, D., Dexter, T. M., Lord, B. I., Wright, E. G. & Lajtha, L. J. Blood 55, 931–936 (1980).

    CAS  Google Scholar 

  3. Pragnell, I. B. et al. Blood 72, 196–201 (1988).

    CAS  PubMed  Google Scholar 

  4. Till, J. E. & McCulloch, E. A. Radiation Res. 14, 213–222 (1961).

    Article  ADS  CAS  Google Scholar 

  5. Lord, B. I., Mori, K. S., Wright, E. G. & Lajtha, L. G. Br. J. Haematol. 34, 441–445 (1976).

    Article  CAS  Google Scholar 

  6. Wright, E. G. & Lorimore, S. A. Cell Tissue Kinet. 20, 191–203 (1987).

    CAS  PubMed  Google Scholar 

  7. Ralph, P., Prichard, J. & Cohn, M. J. Immun. 114, 898–905 (1975).

    CAS  PubMed  Google Scholar 

  8. Wolpe, S. D. et al. J. exp. Med. 167, 571–581 (1988).

    Article  Google Scholar 

  9. Davatelis, G. et al. J. exp. Med. 167, 1939–1944 (1988).

    Article  CAS  Google Scholar 

  10. Sherry, B. et al. J. exp. Med. 168, 2251–2259 (1988).

    Article  CAS  Google Scholar 

  11. Saiki, R. K. et al. Science 330, 1350–1354 (1985).

    Article  ADS  Google Scholar 

  12. Yang, Y. C. et al. Cell 47, 3–10 (1986).

    Article  CAS  Google Scholar 

  13. Frindel, E. & Guigon, M. Expl Hematol. 5, 74–76 (1977).

    CAS  Google Scholar 

  14. Lenfant, M. et al. Proc. natn. Acad. Sci. U.S.A. 86, 779–782 (1989).

    Article  ADS  CAS  Google Scholar 

  15. Lord, B. I., Mori, K. J. & Wright, E. G. Biomedicine 27, 223–226 (1977).

    CAS  PubMed  Google Scholar 

  16. Wolpe, S. D. & Cerami, A. FASEB J. 3, 2565–2573 (1989).

    Article  CAS  Google Scholar 

  17. Wright, E. G., Sheridan, P. & Moore, M. A. S. Leukaemia Res. 4, 309–319 (1980).

    Article  CAS  Google Scholar 

  18. Lord, B. I. & Wright, E. G. in Maturation Factors and Cancer (ed. Moore, M. A. S) 323–333 (Raven, New York 1982).

    Google Scholar 

  19. Hrynuik, W. & Levine, M. N. J. clin. Oncol. 4, 1162–1166 (1986).

    Article  Google Scholar 

  20. Criswold, D. P. Jr et al. Cancer Res. 47, 2323–2327 (1987).

    Google Scholar 

  21. Spangrude, G. J., Heimfield, S. & Weissman, I. L. Science 241, 58–62 (1988).

    Article  ADS  CAS  Google Scholar 

  22. Lord, B. I. & Spooncer, E. Lymphokine Res. 5, 59–72 (1986).

    CAS  PubMed  Google Scholar 

  23. Ploemacher, R. E. & Brons, N. H. C. Expl Hematol. 16, 27–32 (1988).

    CAS  Google Scholar 

  24. Szilvany, S. L., Lansdorp, P. M., Humphries, R. K., Eaves, A. C. & Eaves, C. J. Blood 74, 930–939 (1989).

    Google Scholar 

  25. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  Google Scholar 

  26. Morrissey, J. H. Analyt. Biochem. 117, 307–310 (1981).

    Article  CAS  Google Scholar 

  27. Wolpe, S. D. et al. Proc. natn. Acad. Sci. U.S.A. 86, 612–616 (1989).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Beatson Institute for Cancer Research, Garscube Estate, Glasgow, G61 1BD, UK

    G. J. Graham, N. M. Wilkie & I. B. Pragnell

  2. MRC Radiobiology Unit, Chilton, Oxon, OX11 ORD, UK

    E. G. Wright & S. Lorimore

  3. Genetics Institute, 87 Cambridge Park Drive, Cambridge, Massachusetts, 02140, USA

    R. Hewick , S. D. Wolpe & D. Donaldson

Authors
  1. G. J. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. G. Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Hewick
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. D. Wolpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. M. Wilkie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Donaldson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Lorimore
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. I. B. Pragnell
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Graham, G., Wright, E., Hewick , R. et al. Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. Nature 344, 442–444 (1990). https://doi.org/10.1038/344442a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/344442a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing