Skip to main content
SpringerLink
Log in

In-vitro hematological toxicity prediction by colony-forming cell assays

  • Mini Review
  • Published:
Toxicology and Environmental Health Sciences Aims and scope Submit manuscript

Abstract

Hematotoxicology is concerned with the adverse effects of xenobiotics on hematopoietic processes in a living system. In vitro tests for hematotoxicity have been applied in toxicity assessment of chemicals, drugs, food supplements and environment related studies. Hematopoietic Progenitor Colony-Forming Cell (CFC) assays and Stromal Cell Assays (also called as Non-hematopoietic Progenitor Assays) are already being used to detect hematological toxicities induced by different contaminants. These in vitro tests have been very useful in reducing the number of animals required for hematotoxicity testing. In this review, applications, limitations and future prospective of in vitro tests for hematotoxicity with emphasis on the techniques involved in the Colony forming unit culture systems are described.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Attar, E. C. & Scadden, D. T. Regulation of hematopoietic stem cell growth Leukemia 18, 1760–1768 (2004).

    Article  CAS  PubMed  Google Scholar 

  2. Gordon, M. Y. Human haemopoietic stem cell assays. Blood Rev. 7, 190–197 (1993).

    Article  CAS  PubMed  Google Scholar 

  3. Gordon, M. Y. Origin and development of neutrophils in Immunopharmacology of neutrophils (eds Hellewell, P. G. & Williams, T. J.) 5–26 (Academic Press, Ltd. London, United Kingdom, 1994).

  4. Miller, C. L. & Eaves, C. J. Expansion in vitro of adult murine hematopoietic stem cells with transplantable lympho-myeloid reconstituting ability. Proc. Natl. Acad. Sci. 94, 13648–13653 (1997).

    Article  CAS  PubMed  Google Scholar 

  5. Brandt, J., Briddell, R. A., Srour, E. F., Leemhuis, T. B. & Hoffman, R. Role of c-kit ligand in the expansion of human hematopoietic progenitor cells. Blood 79, 634–641 (1992).

    CAS  PubMed  Google Scholar 

  6. Bryder, D. & Jacobsen, S. E. Interleukin-3 supports expansion of longterm multilineage repopulating activity after multiple stem cell divisions in vitro. Blood 96, 1748–1755 (2000).

    CAS  PubMed  Google Scholar 

  7. Castro-Malaspina, H., Gay, R. E., Resnick, G., Kapoor, N. & Meyers, P. et al. Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 56, 289–301 (1980).

    CAS  PubMed  Google Scholar 

  8. Prockop, D. J. Marrow stromal cells as stem cells for non-hematopoietic tissues. Science 276, 71–74 (1997).

    Article  CAS  PubMed  Google Scholar 

  9. Piersma, A. H., Brockbank, K. G. M., Ploemacher, R. E., Van Vilet, E. & Brakel-van Peer, K. M. J. et al. Characterization of fibroblastic stromal cells from murine bone marrow. Exp. Hematol. 13, 237–243 (1985).

    CAS  PubMed  Google Scholar 

  10. Owen, M. E. & Friedenstein, A. J. Stromal stem cells: marrow-derived osteogenic precursors. Cell and Molecular Biology of Vertebrate Hard Tissues: Ciba Foundation Symposium, Chichester, U.K. 42–60 (1988).

    Google Scholar 

  11. Caplan, A. I. Mesenchymal stem cells. J. Orthop. Res. 9, 641–650 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Pereira, R. F., O’Hara, M. D., Laptev, A. V., Halford, K. W. & Pollard, M. D. et al. Marrow stromal cells as a source of progenitor cells for non-hematopoietic tissues in transgenic mice with a phenotype of osteogenesis imperfecta. Proc. Natl. Acad. Sci. 95, 1142–1147 (1988).

    Article  Google Scholar 

  13. Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E. & Stornaiuolo A. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530 (1988).

    Article  Google Scholar 

  14. Augusto, P., Beatriz, A., Bayo, M., Bueren, J. & Brantom P. et al. In Vitro Tests for Haematotoxicity: Prediction of Drug induced Myelosuppression by the CFUGM Assay. ATLA 30, 75–79 (2002).

    Google Scholar 

  15. Pessina, A., Albella, B., Bayo, M., Bueren, J. & Brantom, P. Application of the CFU-GM assay to predict acute drug-induced neutropenia: an international blind trial to validate a prediction model for the maximum tolerated dose (MTD) of myelosuppressive xenobiotics. Toxicol. Sci. 75, 355–367 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Parchment, R. E., Gordon, M., Grieshaber, C. K., Sessa, C. & Volpe, D. et al. Predicting hematological toxicity (myelosuppression) of cytotoxic drug therapy from in vitro tests. Ann. Oncol. 9, 357–364 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Balls, M. et al. Practical aspects of the validation of toxicity test procedures: The report and recommendations of ECVAM workshop 5. ATLA 23, 129–147 (1995).

    Google Scholar 

  18. Curren, R. D. et al. The role of prevalidation and validation in the development, validation and acceptance of alternative methods. ECVAM Prevalidation Task Force Report 1. ATLA 23, 409–470 (1995).

    Google Scholar 

  19. Du, D. L., Volpe, D. A., Grieshaber, C. K. & Murphy, M. J. Jr. Effects of L-phenylalanine mustard and Lbuthionine sulfoximine on murine and human haematopoietic cells in vitro. Cancer Res. 50, 4038–4043 (1990).

    CAS  PubMed  Google Scholar 

  20. Schmitt, T. M. & Zuniga-Pflucker, J. C. Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro. Immunity 17, 749–756 (2002).

    Article  CAS  PubMed  Google Scholar 

  21. Whitlock, C. A. & Witte, O. N. Long-term culture of B lymphocytes and their precursors from murine bone marrow. Proc. Natl. Acad. Sci. 79, 3608–3612 (1982).

    Article  CAS  PubMed  Google Scholar 

  22. Grever, M. R. & Gneshaber, C. K. 1997. Toxicology by organ system in Cancer Medicine (eds Bast, R. C., Kufe, D. W., Pollock, R. E., Weichselbaum, R. R., Holland, J. F. et al.) 4th edition (Lea and Febiger, Philadelphia, 1997).

  23. Pessina, A., Bonomi, A., Baglio, C., Cavicchini, L. & Gribaldo, L. Refinement and optimisation of the rat CFU-GM assay to incorporate the use of cryopreserved bone-marrow cells for in vitro toxicology applications. Altern. Lab. Anim. 37, 417–425 (2009).

    CAS  PubMed  Google Scholar 

  24. Pessina, A. et al. Prevalidation of the rat CFU-GM assay for in vitro toxicology applications. Altern. Lab. Anim. 38, 105–117 (2010).

    CAS  PubMed  Google Scholar 

  25. Erickson-Miller, C. L. et al., Differential toxicity of camptothecin, topotecan and 9-aminocamptothecin to human, canine, and murine myeloid progenitors (CFUGM) in vitro. Cancer Chemotherapy and Pharmacology 39, 467–472 (1997).

    Article  CAS  PubMed  Google Scholar 

  26. Liu, Y. X., Yue, W., Ji, L., Nan, X., & Pei, X. T. Production of erythriod cells from human embryonic stem cells by fetal liver cell extract treatment. BMC Developmental Biology 10, 85 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Akiyama, K., You, Y. O., Yamaza, T., Chen, C. & Tang, L. et al. Characterization of bone marrow derived mesenchymal stem cells in suspension. Stem Cell Research & Therapy 3, 40 (2012).

    Article  CAS  Google Scholar 

  28. Abnosi, M. H. & Jafari, Y. Z. Low dose and long term toxicity of sodium arsenite caused caspase dependent apoptosis based on morphology and biochemical character. Cell J. 14, 161–170 (2012).

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Scherzed, A., Hackenberg, S., Froelich, K., Rak, K. & Technau, A. Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro. Toxicol Lett. 218, 207–214 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Rahnama, R., Wang, M., Dang, A. C., Kim, H. T. & Kuo, A. C. Cytotoxicity of local anesthetics on human mesenchymal stem cells. J. Bone Joint Surg. Am. 95, 132–137 (2013).

    Article  PubMed  Google Scholar 

  31. Mets, T. & Verdonk, G. In vitro aging of human bone marrow-derived stromal cells. Mech. Ageing. Dev. 16, 81–89 (1981).

    Article  CAS  PubMed  Google Scholar 

  32. Friedenstein, A. J., Chailakhyan, R. K. & Gerasimov, U. V. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation diffusion chambers. Cell Tissue Kinet. 20, 263–272 (1987).

    CAS  PubMed  Google Scholar 

  33. Parent-Massin, D. Relevance of clonogenic assays in food haematotoxicology in Progress in the Reduction, Refinement and Replacement of Animal Experimentation, Development in Animal and Veterinary Sciences (eds Balls, M., Zeller, A. M., Halder, M.) 31, 709–714 (Elsevier Science, 2000).

    Google Scholar 

  34. Diodovich, C. et al. Gene and protein expressions in human cord blood cells after exposure to acrylonitrile. J. Biochem. Mol. Toxicol. 19, 204–212 (2003).

    Article  Google Scholar 

  35. Diodovich, C. et al. Response of human cord blood cells to styrene exposure: evaluation of its effects on apoptosis and gene expression by genomic technology. Toxicol. 200, 145–157 (2004).

    Article  CAS  Google Scholar 

  36. Diodovich, C. et al. Sensitivity of human cord blood cells to tetrachloroethylene: cellular and molecular endpoints. Arch. Toxicol. 79, 508–514 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Song, H., Vita, M., Sallam, H., Tehranchi, R. & Nilsson, C. Effect of the Cdk-inhibitor roscovitine on mouse hematopoietic progenitors in vivo and in vitro. Cancer Chemother. Pharmacol. 60, 841–849 (2007).

    CAS  Google Scholar 

  38. Molyneux, G., Gibson, F. M., Chen, C. M., Marway, H. K. & McKeaq, S. et al. The haematotoxicity of azathioprine in repeat dose studies in the female CD-1 mouse. Int. J. Exp. Pathol. 89, 138–158 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Grande, T. & Bueren, J. A. Analysis of the hematopoiesis in mice irradiated with 500mGy of X-rays at different stages of development. Radiation Res. 143, 327–333 (1995).

    Article  CAS  PubMed  Google Scholar 

  40. Outlook 2010. Tufts Center for Study of Drug Development report.

    Google Scholar 

  41. May, J. E., Morse, H. R., Xu, J. & Donalson, C. Development of a novel, physiologically relevant cytotoxicity model: application to the study of chemotherapeutic damage to mesenchymal stromal cells. Toxicol. Appl. Pharmacol. 263, 374–389 (2012).

    Article  CAS  PubMed  Google Scholar 

  42. Parent-Massin, D., Hymery, N. & Sibiril, Y. Stem cells in myelotoxicity. Toxicol. 267, 112–117 (2010).

    Article  CAS  Google Scholar 

  43. Rich, I. N. & Hall, K. M. Validation and development of a predictive paradigm for hematoxicology using a multifunctional bioluminescence colony-forming proliferation assay. Toxicol. Sci. 87, 427–441 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Toxicology CSIR-Central Drug Research Institute, Lucknow, 226031, India

    Navneet Kumar Yadav, Pooja Shukla, Ankur Omer & Rama Kant Singh

Authors
  1. Navneet Kumar Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pooja Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ankur Omer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rama Kant Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rama Kant Singh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yadav, N.K., Shukla, P., Omer, A. et al. In-vitro hematological toxicity prediction by colony-forming cell assays. Toxicol. Environ. Health Sci. 5, 169–176 (2013). https://doi.org/10.1007/s13530-013-0172-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13530-013-0172-7

Keywords

Search

Navigation