Skip to main content
Log in

Confocal microscopy of cells implanted into tissue blocks: Cell migration in long-term histocultures

  • Cellular Models
  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Summary

In three-dimensional tissues in vivo, cells find themselves in a unique, heterogeneous microenvironment among various cellular and noncellular elements. Cells are greatly affected by and contribute to their physical and chemical microenvironments. However, live cells are currently studied predominantly in homogeneous monolayer cultures where newly established contacts might be fundamentally different from contacts in vivo. Several systems have been suggested to simulate the three-dimensional environment of real tissue. In this report, we describe a new system for studying cell behavior inside real tissues in vitro. By fluorescently labeling mouse tumor cells, then implanting them into cultured tissue blocks (histocultures), we have observed cellular location and followed their locomotion, within tissues in vitro for days. We discuss the potential of the described system for studying different aspects of cell behavior in a nativelike microenvironment.

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

  • Baibakov, B. A.; Frank, G. A.; Sergeeva, N. S., et al. In vivo growth pattern of human lung tumors in three-dimensional histoculture. In Vitro Cell. Dev. Biol. 27:897–899; 1991.

    Article  Google Scholar 

  • Bracke, M.; Romijn, M.; Vakaef, L., et al. The use of spheroids in the study of invasion. In: Bjerkvig, R., ed. Spheroid culture in cancer research. Boca Raton, FL: CRC Press; 1992:73–106.

    Google Scholar 

  • Carrel, A. On the permanent life of tissues outside of the organism. J. Exp. Med. 15:516–528; 1912.

    Article  Google Scholar 

  • Coble, A. J.; Leader, J. P.; Spring, K. R. Microscope interferometry of necturus gallbladder epithelium. In: Bradley, S. E.; Purcell, E. F., eds. The paracellular pathway. New York: Josiah Macy, Jr. Foundation; 1992:270–303.

    Google Scholar 

  • Evans, C. W. The metastatic cell behavior and biochemistry. London: Chapman and Hall; 1991:293–330.

    Google Scholar 

  • Freeman, A. E.; Hoffman, R. M. In vivo-like growth of human tumors in vitro. Proc. Natl. Acad. Sci. USA 83:2694–2698; 1986.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, R. G. Observations on the living developing nerve fiber. Proc. Soc. Exp. Biol. Med. 4:140–143; 1907.

    Google Scholar 

  • Hell, S.; Reiner, G.; Cremer, C., et al. Aberrations in confocal fluorescence microscopy induced by mismatches in refractive index. J. Microsc. 169:391–405; 1993.

    Google Scholar 

  • Hoffman, R. M. Three-dimensional gel-supported native-state histoculture for evaluation of tumor-specific pharmacological activity: principles, practice and possibilities. J. Cell Pharmacol. 2:189–202; 1991.

    CAS  Google Scholar 

  • Le Douarin, N. M.; Dupin, E. Cell lineage analysis in neural crest ontogeny. J. Neurobiol. 24:146–161; 1993.

    Article  PubMed  Google Scholar 

  • Leighton, J. Contributions of tissue culture studies to an understanding of the biology of cancer: a review. Cancer Res. 17:929–941; 1957.

    PubMed  CAS  Google Scholar 

  • Leighton, J.; Kalla, R. L.; Turner, J. M., Jr., et al. Pathogenesis of tumor invasion. II. Aggregate replication. Cancer Res. 20:575–597; 1960.

    PubMed  CAS  Google Scholar 

  • Li, L.; Margolis, L. B.; Hoffman, R. M. Skin toxicity determined in vitro by three-dimensional native-state histoculture. Proc. Natl. Acad. Sci. USA 88:1908–1912; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Li, L.; Margolis, L. B.; Lishko, V., et al. Product-delivering liposomes specially target hair follicles in histocultured intact skin. In Vitro Cell. Dev. Biol. 28:679–684; 1992a.

    Article  Google Scholar 

  • Li, L.; Margolis, L. B.; Paus, R., et al. Hair shaft elongation, follicle growth, and spontaneous regression in long-term, gelatin sponge-supported histoculture of human scalp skin. Proc. Natl. Acad. Sci. USA 89:8764–8768; 1992b.

    Article  PubMed  CAS  Google Scholar 

  • Lund-Johanesen, M.; Bjerkvig, R.; Rucklidge, G. J. Tumor spheroids from monolayer cultures. In: Bjerkvig, R., ed. Spheroid culture in cancer research. Boca Raton, FL: CRC Press; 1992:3–18.

    Google Scholar 

  • Moscona, A. A. Surface specification of embryonic cells: Lectin receptors, cell recognition and specific cell ligands. In: Moscona, A. A., ed. The cell surface in development. New York: John Wiley & Sons; 1974:67–100.

    Google Scholar 

  • O’Rourke, W. A.; Dailey, M. E.; Smith, S. J., et al. Diverse migration pathways in the developing cerebral cortex. Science 258:299–302; 1992.

    Article  PubMed  CAS  Google Scholar 

  • Raus, P.; Jones, V. M. D. A method for obtaining suspensions of living cells from the fixed tissues and for the plating out of individual cells. J. Exp. Med. 23:549–555; 1916.

    Article  Google Scholar 

  • Stetler-Stevenson, W. G. Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev. 9:289–303; 1991.

    Google Scholar 

  • Sutherland, R. M. Cell and environmental interactions in tumormicroregions: the multicell spheroid model. Science 240:177–184; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Tsien, R. Y.; Poenie, M. Fluorescence ratio imaging: a new window into intracellular came signaling. TIBS 11:150–156; 1986.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Margolis, L.B., Glushakova, S.E., Baibakov, B.A. et al. Confocal microscopy of cells implanted into tissue blocks: Cell migration in long-term histocultures. In Vitro Cell Dev Biol - Animal 31, 221–226 (1995). https://doi.org/10.1007/BF02639437

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02639437

Key words

Navigation