Skip to main content

Engineering Quasi-Vivo® in Vitro Organ Models

  • Chapter
New Technologies for Toxicity Testing

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 745))

Abstract

Cell culture is the workhorse of biologists, toxicologists, tissue engineers and a whole host of research fields in both academia and industry. Having explored individual molecular mechanisms inside cells for decades using traditional cell culture techniques, researchers have only just begun to appreciate that the intricate interconnectivity between cells and cellular networks as well as with the external environment is far more important to cellular orchestration than are single molecular events inside the cell. For example many questions regarding cell, tissue, organ and system response to drugs, environmental toxins, stress and nutrients cannot possibly be answered by concentrating on the minutiae of what goes on in the deepest recesses of single cells. New models are required to investigate cellular cross-talk between different cell types and to construct complex in-vitro models to properly study tissue, organ and system interaction without resorting to animal experiments. This chapter describes how tissue and organ models can be developed using the Quasi-Vivo® system and discusses how they may be used in drug toxicity studies.

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

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kirkpatrick J, Fuchs S, Hermanns I et al. Cell culture models of higher complexity in tissue engineering and regenerative medicine, Biomaterials 2007; 28(34):5193–5198.

    Article  CAS  Google Scholar 

  2. Zhang S. Beyond the petri dish. Nat Biotechnol 2004; 22(2):151–152.

    Article  PubMed  CAS  Google Scholar 

  3. Cantòn I, Cole DM, Kemp EH et al. Development of a 3D human in vitro skin co-culture model for detecting irritants in real-time. Biotechnol Bioeng 2010; 106(5):794–803.

    Article  PubMed  Google Scholar 

  4. Van de Bovenkamp M, Groothuis GM, Meijer DK et al. Liver fibrosis in vitro: cell culture models and precision-cut liver slices. Toxicol In Vitro 2007; 21(4):545–557.

    Article  PubMed  Google Scholar 

  5. Sung, JH, Esch MB, Shuler ML. Integration of in silico and in vitro platforms for pharmacokineticpharmacodynamic modeling. Expert Opin Drug Metab Toxicol 2010; 6(9):1063–1081.

    Article  PubMed  CAS  Google Scholar 

  6. Mazzei D, Guzzardi MA, Giusti S et al. A low shear stress modular bioreactor for connected cell culture under high flow rates. Biotechnol Bioeng 2010; 106(1):127–137.

    PubMed  CAS  Google Scholar 

  7. Di Nardo P, Minieri M, Ahluwalia A. Engineering the stem cell niche and the differentiative micro and macroenvironment: technologies and tools for applying biochemical, physical and structural stimuli and their effects on stem cells. In: Artmann GM, Minger S, Hescheler J, eds. Stem Cell Engineering: Principles and Applications. Heidelberg: Springer-Verlag, 2010:41–48.

    Google Scholar 

  8. Smith MK, Mooney DJ. Hypoxia leads to necrotic hepatocyte death. J Biomed Mater Res A 2007; 80(3):520–529.

    PubMed  Google Scholar 

  9. Swartz MA, Fleury ME. Interstitial flow and its effects in soft tissues. Annu Rev Biomed Eng 2007; 9:229–256.

    Article  PubMed  CAS  Google Scholar 

  10. Pedersen JA, Boschetti F, Swartz MA. Effects of extracellular fiber architecture on cell membrane shear stress in a 3D fibrous matrix. J Biomech 2007; 10:1484–1492.

    Article  Google Scholar 

  11. Wang DM, Tabell JM. Modeling interstitial flow in an artery wall allows estimation of wall shear stress on smooth muscle cells. Trans ASME 1995; 117:358–363.

    Article  CAS  Google Scholar 

  12. Tilles AW, Baskaran H, Roy P et al. Effects of oxygenation and flow on the viability and function of rat hepatocytes cocultured in a microchannel flat-plate bioreactor. Biotechnol Bioeng 2001; 73(5):379–389.

    Article  PubMed  CAS  Google Scholar 

  13. Vinci B, Duret C, Klieber S et al. Medium flow stimulates expression and activity of detoxication genes in primary human hepatocytes in a multicompartment modular bioreactor. Biotech J 2011;6(5):554–564.

    Article  CAS  Google Scholar 

  14. Wei CW, Cheng JY, Young TH. Elucidating in vitro cell-cell interaction using a microfluidic coculture system. Biomed Microdevices 2006; 8(1):65–71.

    Article  PubMed  CAS  Google Scholar 

  15. Tirella A, Marano M, Vozzi F et al. A microfluidic gradient maker for toxicity testing of bupivacaine and lidocaine. Toxicol in Vitro 2008; 22:1957–1964.

    Article  PubMed  CAS  Google Scholar 

  16. McBeath R, Pirone DM, Nelson CM et al. Cell shape, cytoskeletal tension and RhoA regulate stem cell lineage commitment. Dev Cell 2004; 6(4):483–495.

    Article  PubMed  CAS  Google Scholar 

  17. Francis K, Palsson BO. Effective intercellular communication distances are determined by the relative time constants for cyto/chemokine secretion and diffusion. Proc Natl Acad Sci USA 1997; 94:12258–12262.

    Article  PubMed  CAS  Google Scholar 

  18. Kilian KA, Bugarija B, Lahn BT et al. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Natl Acad Sci USA 2010; 107(11):4872–4877.

    Article  PubMed  CAS  Google Scholar 

  19. Vozzi F, Heinrich JM, Bader A et al. Connected culture of murine hepatocytes and HUVEC in a multicompartmental bioreactor. Tissue Eng Part A 2009; 15(6):1291–1299.

    Article  PubMed  CAS  Google Scholar 

  20. Guzzardi MA, Vozzi F, Ahluwalia A. Study of the cross-talk between hepatocytes and HUVEC using a novel multi compartmental bioreactor: a comparison between connected cultures and co-cultures. Tissue Eng Part A 2009; 15(11):3635–3644.

    Article  PubMed  CAS  Google Scholar 

  21. Guillouzo A. Liver cell models in vitro toxicology. Environ Health Perspect 1998; 106:551–532.

    Article  Google Scholar 

  22. Nahmias Y, Berthiaume F, Yarmush ML. Integration of technologies for hepatic tissue engineering. Adv Biochem Eng Biotechnol 2007; 103:309–329.

    PubMed  Google Scholar 

  23. West BG, Brown JH, eds. Scaling in Biology. New York: Oxford University Press, 2000.

    Google Scholar 

  24. Pichard L, Raulet E, Fabre G et al. Human hepatocyte culture. Methods Mol Biol 2006; 320:283–293.

    PubMed  Google Scholar 

  25. Lindstedt SL, Calder WA. Body size, physiological time and longevity of homeothermic animals. The Q Rev Biol 1981; 56(1):1–16.

    Article  Google Scholar 

  26. Vinci B, Cavallone D, Mazzei D et al. In vitro liver model using microfabricated scaffolds in a modular bioreactor. Biotechnol J 2010; 5(2):232–241.

    Article  PubMed  CAS  Google Scholar 

  27. Guillouzo A, Guguen-Guillouzo C. Evolving concepts in liver tissue modeling and implications for in vitro toxicology. Expert Opin Drug Metab Toxicol 2008; 1279–1294.

    Google Scholar 

  28. Boelsterli UA. Diclofenac-induced liver injury: a paradigm of idiosyncratic drug toxicity. Toxicol Appl Pharmacol 2003; 192(3):307–322.

    Article  PubMed  CAS  Google Scholar 

  29. Roque B, Ponsoda X, Jover R et al. Diclofenac toxicity to hepatocytes: a role for drug metabolism in cell toxicity. J Pharmacol Exp Ther 1999; 288(1):65–72.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arti Ahluwalia .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Landes Bioscience and Springer Science+Business Media

About this chapter

Cite this chapter

Sbrana, T., Ahluwalia, A. (2012). Engineering Quasi-Vivo® in Vitro Organ Models. In: Balls, M., Combes, R.D., Bhogal, N. (eds) New Technologies for Toxicity Testing. Advances in Experimental Medicine and Biology, vol 745. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3055-1_9

Download citation

Publish with us

Policies and ethics