Skip to main content

Advertisement

SpringerLink
Log in

A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells

  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

The mesenchymal stromal cell line SR-4987 has been established in our laboratory from the bone marrow of BDF/1 mice. Recent information on mesenchymal stem cells biology and the need to deal with well-characterized cell lines suggest to critically consider the existent data on this cell line by updating them with new investigations on growth parameters, in vitro plasticity, and drug sensitivity to anti-cancer, anti-inflammatory, and a histone deacetylase inhibitor. SR-4987 cells show a population doubling time of 24.5 ± 5.4 h, a plating efficiency of 2.87 ± 1.19%, and under stimulation maintain only in part their multipotency by differentiating towards chondro-osteogenic lineages but not into adipogenic. Surprisingly, these mesenchymal stromal cells differentiate spontaneously into osteoblast-like cells and this is significantly stimulated by valproic acid. SR-4987 cells show a dramatic resistance to paclitaxel (PTX) with a resistance index of 39.6 times (evaluated versus MOLT-4 leukemia) and of 68.2 (versus HT-29 colorectal carcinoma). SR-4987 resistance is reversed by verapamil and correlates with high expression of P-glycoprotein that is down-modulated by PTX. Taken together, our results indicated that SR-4987 line is a very interesting cell model useful to investigate both drug sensitivity resistance and physiopathological aspects related to mesenchymal cell function.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Burns BS, Edin ML, Lester GE, Tuttle HG, Wall ME, Wani MC, et al. Selective drug resistant human osteosarcoma cell lines. Clin Orthop Relat Res. 2001;383:259–67.

    Article  PubMed  Google Scholar 

  • Chang JK, Li CJ, Wu SC, Yeh CH, Chen CH, Fu YC, et al. Effects of anti-inflammatory drugs on proliferation, cytotoxicity and osteogenesis in bone marrow mesenchymal stem cells. Biochem Pharmacol. 2007;74:1371–82.

    Article  PubMed  CAS  Google Scholar 

  • Cho HH, Park HT, Kim YJ, Bae YC, Suh KT, Jung JS. Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J Cell Biochem. 2005;96:533–42.

    Article  PubMed  CAS  Google Scholar 

  • Dennis JE, Merriam A, Awadallah A, Yoo JU, Johnstone B, Caplan AI. A quadripotential mesenchymal progenitor cell isolated from the marrow of an adult mouse. J Bone Miner Res. 1999;14:700–9.

    Article  PubMed  CAS  Google Scholar 

  • Fogh J, Trempe G. New human tumor cell lines. In: Fogh J, editor. Human tumor cells in vitro. New York: Plenum; 1975. p. 115–41.

    Google Scholar 

  • Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV. Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol. 1966;16:381–90.

    PubMed  CAS  Google Scholar 

  • Gribaldo L, Catalani P, Erminio M. Metabolism of doxorubicin in long-term bone marrow cultures and SR-4987 stromal established cell line. Drug Metab Drug Interact. 1999;15:279–91.

    CAS  Google Scholar 

  • Haynesworth SE, Baber MA, Caplan AI. Cell surface antigens on human marrow-derived mesenchymal cells are detected by monoclonal antibodies. Bone. 1992;13:69–80.

    Article  PubMed  CAS  Google Scholar 

  • Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238:265–72.

    Article  PubMed  CAS  Google Scholar 

  • Kellinsalmi M, Parikka V, Risteli J, Hentunen T, Leskelä HV, Lehtonen S, et al. Inhibition of cyclooxygenase-2 down-regulates osteoclast and osteoblast differentiation and favours adipocyte formation in vitro. Eur J Pharmacol. 2007;572:102–10.

    Article  PubMed  CAS  Google Scholar 

  • McAteer JA, Devis J. Basic cell culture technique and the maintenance of cell lines. In: Davis JM, editor. Basic cell culture. Oxford: Oxford University Press; 1994. p. 93–148.

    Google Scholar 

  • Minowada J, Onuma T, Moore GE. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972;49:891–5.

    PubMed  CAS  Google Scholar 

  • Mossman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Meth. 1983;65:55–63.

    Article  Google Scholar 

  • Opavsky R, Haviernik P, Jurkovicova D, Garin MT, Copeland NG, Gilbert DJ, et al. Molecular characterization of the mouse Tem1/endosialin gene regulated by cell density in vitro and expressed in normal tissues in vivo. J Biol Chem. 2001;276:38795–807.

    Article  PubMed  CAS  Google Scholar 

  • Orr GA, Verdier-Pinard P, McDaid H, Horwitz SB. Mechanisms of Taxol resistance related to microtubules. Oncogene. 2003;22:7280–95.

    Article  PubMed  CAS  Google Scholar 

  • Parekh H, Wiesen K, Simpkins H. Acquisition of taxol resistance via P-glycoprotein- and non-P-glycoprotein-mediated mechanisms in human ovarian carcinoma cells. Biochem Pharmacol. 1997;53:461–70.

    Article  PubMed  CAS  Google Scholar 

  • Pessina A, Mineo E, Neri MG, Gribaldo L, Colombi R, Brambilla P, et al. Establishment and characterization of a new murine cell line (SR-4987) derived from marrow stromal cells. Cytotechnology. 1992;8:93–102.

    Article  PubMed  CAS  Google Scholar 

  • Pessina A, Gribaldo L, Mineo E, Neri MG. In vitro short-term and long-term cytotoxicity of fluoroquinolones on murine cell lines. Ind J Exp Biol. 1994;32:113–8.

    CAS  Google Scholar 

  • Pessina A, Piccirillo M, Mineo E, Tassi E, Brambilla P, Neri MG. A simple quantitative bioassay for basic fibroblast growth factor using SR-4987 cells as target. Methods Mol Cell Biol. 1995;5:230–6.

    Google Scholar 

  • Pessina A, Neri MG, Mineo E, Piccirillo M, Gribaldo L, Brambilla P, et al. Expression of B cell markers on SR-4987 cells derived from murine marrow stroma. Exp Hematol. 1997;25:536–41.

    PubMed  CAS  Google Scholar 

  • Pessina A, Mineo E, Neri MG, Piccirillo M, Valore L, Giuliani A. SR-4987 and L1210 cell lines: two models in which cholera toxin susceptibility does not correlate with cAMP accumulation and ganglioside content. Cell Mol Biol. 1998;44:933–40.

    PubMed  CAS  Google Scholar 

  • Pessina A, Piccirillo M, Mineo E, Catalani P, Gribaldo L, Marafante E, et al. Role of SR-4987 stromal cells in the modulation of doxorubicin toxicity to in vitro granulocyte-macrophage progenitors (CFU-GM). Life Sci. 1999;655:513–23.

    Article  Google Scholar 

  • Pessina A, Eletti B, Croera C, Savalli N, Diodovich C, Gribaldo L. Pancreas developing markers expressed on human mononucleated umbilical cord blood cells. Biochem Biophys Res Commun. 2004;323:315–22.

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284:143–7.

    Article  PubMed  CAS  Google Scholar 

  • Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Epidemiol. 1938;27:493–7.

    Google Scholar 

  • Røsland GV, Svendsen A, Torsvik A, Sobala E, McCormack E, Immervoll H, et al. Long-term cultures of bone marrow-derived human mesenchymal stem cells frequently undergo spontaneous malignant transformation. Cancer Res. 2009;69:5331–9.

    Article  PubMed  Google Scholar 

  • Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature. 1979;277:665–7.

    Article  PubMed  CAS  Google Scholar 

  • Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med. 2001;7:584–90.

    Article  PubMed  CAS  Google Scholar 

  • Takagi M. Cell processing engineering for ex-vivo expansion of hematopoietic cells. J Biosci Bioeng. 2005;99:189–96.

    Article  PubMed  CAS  Google Scholar 

  • Takagi M, Sasaki T, Yoshida T. Spatial development of the cultivation of a bone marrow stromal cell line in porous carriers. Cytotechnology. 1999;31:225–31.

    Article  PubMed  CAS  Google Scholar 

  • Tallheden T, Dennis JE, Lennon DP, Sjögren-Jansson E, Caplan AI, Lindahl A. Phenotypic plasticity of human articular chondrocytes. J Bone Joint Surg Am. 2003;85:93–100.

    PubMed  Google Scholar 

  • Tropel P, Noe D, Platet N, Legrand P, Benabid AL, Berbera F. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res. 2004;295:395–406.

    Article  PubMed  CAS  Google Scholar 

  • Ulmanen M, Birr E, Hietala O, Lindholm TS. Determination of the biological activity of BMPs in cell cultures is unreliable. In: Lindholm TS, editor. Advances in skeletal reconstruction using bone morphogenetic proteins. Singapore: World Scientific; 2002. p. 53–61.

    Chapter  Google Scholar 

  • Wang Y, Chen X, Zhu W, Zhang H, Hu S, Cong X. Growth inhibition of mesenchymal stem cells by aspirin: involvement of the WNT/beta-catenin signal pathway. Clin Exp Pharmacol Physiol. 2006;33:696–701.

    Article  PubMed  CAS  Google Scholar 

  • Yamaza T, Miura Y, Bi Y, Liu Y, Akiyama K, Sonoyama W, et al. Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents. PLoS ONE. 2008;3:e2615.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Public Health–Microbiology–Virology, University of Milan, Via Pascal 36, 20133, Milan, Italy

    Augusto Pessina, Francesca Sisto, Valentina Coccè, Loredana Cavicchini & Arianna Bonomi

  2. Fondazione IRCCS Istituto Neurologico Besta, Milan, Italy

    Emilio Ciusani

  3. IHCP, Joint Research Centre, Ispra, VA, Italy

    Laura Gribaldo

Authors
  1. Augusto Pessina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Sisto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valentina Coccè
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Loredana Cavicchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emilio Ciusani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura Gribaldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Arianna Bonomi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Augusto Pessina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pessina, A., Sisto, F., Coccè, V. et al. A mesenchymal stromal cell line resistant to paclitaxel that spontaneously differentiates into osteoblast-like cells. Cell Biol Toxicol 27, 169–180 (2011). https://doi.org/10.1007/s10565-010-9179-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-010-9179-x

Keywords

Search

Navigation