Skip to main content

Improved reproducibility in preparing precision-cut liver tissue slices

Cytotechnology volume 61, pages 145–152 (2009)Cite this article

Abstract

Precision-cut liver tissue slices (PCLS) have been used for decades to study pharmacological metabolism as well as toxicology and efficacy of novel substances on primary material under standardized conditions. Slicing of primary liver tissue has been done using different slicing machines. Since there has been great variability in the results, we sought to compare the reproducibility of tissue slices generated using the newly developed Leica VT1200 S vibrating blade microtome with Vibrocheck (LV) and the Krumdieck tissue slicer (KD) which has been the standard apparatus for this application so far. Liver samples from five different species (human, pig, cattle, rat, mouse) were cut and the reproducibility of slice thickness was analyzed by cross sectioning the PCLS. The quality of the sliced tissue was determined via measurement of the ATP content. As a result, we found an improved accuracy and reproducibility of rat, mouse and human tissue slices using the new Leica vibrating blade microtome.

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

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3

References

  • Brendel K, McKee RL, Hruby VJ, Johnson DG, Gandolfi AJ, Krumdieck CL (1987) Precision cut tissue slices in culture: a new tool in pharmacology. Proc West Pharmacol Soc 30:291–293

    CAS  Google Scholar 

  • Fisher RL, Hasal SJ, Sipes IG, Gandolfi AJ, Brendel K (1995) Comparative metabolism and toxicity of dichlorobenzenes in Sprague-Dawley, Fischer-344 and human liver slices. Hum Exp Toxicol 14:414–421

    Article  CAS  Google Scholar 

  • Gandolfi AJ, Wijeweera J, Brendel K (1996) Use of precision-cut liver slices as an in vitro tool for evaluating liver function. Toxicol Pathol 24:58–61

    Article  CAS  Google Scholar 

  • Kirby TO, Rivera A, Rein D, Wang M, Ulasov I, Breidenbach M, Kataram M, Contreras JL, Krumdieck C, Yamamoto M et al (2004) A novel ex vivo model system for evaluation of conditionally replicative adenoviruses therapeutic efficacy and toxicity. Clin Cancer Res 10:8697–8703

    Article  CAS  Google Scholar 

  • Krumdieck CL, dos Santos JE, Ho KJ (1980) A new instrument for the rapid preparation of tissue slices. Anal Biochem 104:118–123

    Article  CAS  Google Scholar 

  • Lerche-Langrand C, Toutain HJ (2000) Precision-cut liver slices: characteristics and use for in vitro pharmaco-toxicology. Toxicology 153:221–253

    Article  CAS  Google Scholar 

  • Olinga P, Meijer DKF, Slooff MJH, Groothuis GMM (1998) Liver slices in in vitro pharmacotoxicology with special reference to the use of human liver tissue. Toxicol In Vitro 12:77–100

    Article  CAS  Google Scholar 

  • Parrish AR, Gandolfi AJ, Brendel K (1995) Precision-cut tissue slices: applications in pharmacology and toxicology. Life Sci 57:1887–1901

    Article  CAS  Google Scholar 

  • Price RJ, Ball SE, Renwick AB, Barton PT, Beamand JA, Lake BG (1998) Use of precision-cut rat liver slices for studies of xenobiotic metabolism and toxicity: comparison of the Krumdieck and Brendel tissue slicers. Xenobiotica 28:361–371

    Article  CAS  Google Scholar 

  • Rots MG, Elferink MG, Gommans WM, Oosterhuis D, Schalk JA, Curiel DT, Olinga P, Haisma HJ, Groothuis GM (2006) An ex vivo human model system to evaluate specificity of replicating and non-replicating gene therapy agents. J Gene Med 8:35–41

    Article  CAS  Google Scholar 

  • Stoff-Khalili MA, Rivera AA, Le LP, Stoff A, Everts M, Contreras JL, Chen D, Teng L, Rots MG, Haisma HJ et al (2006) Employment of liver tissue slice analysis to assay hepatotoxicity linked to replicative and nonreplicative adenoviral agents. Cancer Gene Ther 13:606–618

    Article  CAS  Google Scholar 

  • van de Bovenkamp M, Groothuis GM, Meijer DK, Slooff MJ, Olinga P (2006) Human liver slices as an in vitro model to study toxicity-induced hepatic stellate cell activation in a multicellular milieu. Chem Biol Interact 162:62–69

    Article  Google Scholar 

  • Zimmermann M, Armeanu S, Smirnow I, Kupka S, Wagner S, Wehrmann M, Rots MG, Groothuis GM, Weiss TS, Konigsrainer A et al (2009) Human precision-cut liver tumor slices as a tumor patient-individual predictive test system for oncolytic measles vaccine viruses. Int J Oncol 34:1247–1256

    CAS  Google Scholar 

Download references

Acknowledgment

We are grateful to Leica Biosystems Nussloch GmbH for the provision of a research grant.

Author information

Affiliations

  1. Department of Gastroenterology and Hepatology, University Hospital Tuebingen, Otfried-Mueller-Str. 10, 72076, Tuebingen, Germany

    Martina Zimmermann, Johanna Lampe, Sebastian Lange, Irina Smirnow, Michael Gregor, Michael Bitzer & Ulrich M. Lauer

  2. Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, Tuebingen, Germany

    Alfred Königsrainer

  3. Department of Pathology, University Hospital Tuebingen, Tuebingen, Germany

    Claus Hann-von-Weyhern & Falko Fend

Authors
  1. Martina Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johanna Lampe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sebastian Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Irina Smirnow
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alfred Königsrainer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Claus Hann-von-Weyhern
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Falko Fend
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Michael Gregor
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael Bitzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ulrich M. Lauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ulrich M. Lauer.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zimmermann, M., Lampe, J., Lange, S. et al. Improved reproducibility in preparing precision-cut liver tissue slices. Cytotechnology 61, 145–152 (2009). https://doi.org/10.1007/s10616-009-9246-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10616-009-9246-4

Keywords

  • Primary culture
  • Precision-cut liver slices (PCLS)
  • Leica VT1200 S vibrating blade microtome
  • Krumdieck tissue slicer