Skip to main content

Introduction to 3D Cell Culture

  • Chapter
  • First Online:
Basic Concepts on 3D Cell Culture

Part of the book series: Learning Materials in Biosciences ((LMB))

What You Will Learn in This Chapter

This chapter explains the importance of 3D cell culture and highlights its potential and benefits in comparison to traditional 2D cultivation. Since 3D cell culture is supposed to mimic the in vivo situation, we will also have a close look on the complex composition of the in vivo microenvironment and why 2D cultivation does not resemble the in vivo situation. Furthermore, we will cover the most important approaches for 3D cell culture which are matrix-free and matrix-based cultivation as well as bioprinting. Also, the main applications of 3D cell culture, in vitro tissue or disease models and tissue engineered constructs for tissue repair or regeneration, will be introduced. Finally, you will learn that 3D cell culture has its limitations and challenges when it comes to the analysis and monitoring of 3D cell culture processes.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 69.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 89.99
Price excludes VAT (USA)
  • Compact, lightweight 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

References

  1. Ronfard V, Vertès AA, May MH, Dupraz A, van Dyke ME, Bayon Y. Evaluating the past, present, and future of regenerative medicine: a global view. Tissue Eng Part B Rev. 2017;23(2):199–210. https://doi.org/10.1089/ten.teb.2016.0291.

    Article  PubMed  Google Scholar 

  2. Ledford H. Translational research: 4 ways to fix the clinical trial. Nature. 2011;477(7366):526–8. https://doi.org/10.1038/477526a.

    Article  CAS  PubMed  Google Scholar 

  3. Fernandez-Moure JS. Lost in translation: the gap in scientific advancements and clinical application. Front Bioeng Biotechnol. 2016;4:43. https://doi.org/10.3389/fbioe.2016.00043.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Justice BA, Badr NA, Felder RA. 3D cell culture opens new dimensions in cell-based assays. Drug Discov Today. 2009;14(1–2):102–7. https://doi.org/10.1016/j.drudis.2008.11.006.

    Article  CAS  PubMed  Google Scholar 

  5. Thoma CR, Zimmermann M, Agarkova I, Kelm JM, Krek W. 3D cell culture systems modeling tumor growth determinants in cancer target discovery. Adv Drug Deliv Rev. 2014;69–70:29–41. https://doi.org/10.1016/j.addr.2014.03.001.

    Article  CAS  PubMed  Google Scholar 

  6. O’Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14(3):88–95. https://doi.org/10.1016/S1369-7021(11)70058-X.

    Article  CAS  Google Scholar 

  7. Hynes RO. Cell adhesion: old and new questions. Trends Genet. 1999;15(12):M33–7. https://doi.org/10.1016/S0168-9525(99)01891-0.

    Article  CAS  Google Scholar 

  8. Alberts B, et al. Molecular biology of the cell, vol. 20. 6th ed. Boca Raton: Garland Science; 2014.

    Google Scholar 

  9. Ricard-Blum S. The collagen family. Cold Spring Harb Perspect Biol. 2011;3(1):4978. https://doi.org/10.1101/cshperspect.a004978.

    Article  Google Scholar 

  10. Mithieux SM, Weiss AS. Elastin. Adv Protein Chem. 2005;70:437–61.

    Article  CAS  Google Scholar 

  11. Adams JC, Watt FM. Regulation of development and differentiation by the extracellular matrix. Development. 1993;117(4):1183–98.

    Article  CAS  Google Scholar 

  12. Durbeej M. Laminins. Cell Tissue Res. 2010;339(1):259–68. https://doi.org/10.1007/s00441-009-0838-2.

    Article  CAS  PubMed  Google Scholar 

  13. McKeown SR. Defining normoxia, physoxia and hypoxia in tumours—implications for treatment response. Br J Radiol. 2014;87(1035):20130676. https://doi.org/10.1259/bjr.20130676.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Khorshid F. The effect of the medium viscosity on the cells morphology in reaction of cells to topography-I, pp. 15–17; 2004.

    Google Scholar 

  15. Jedrzejczak-Silicka M. History of cell culture. In: New insights into cell culture technology. London: InTech; 2017.

    Google Scholar 

  16. Vincent JFV. Structural biomaterials. New York: Macmillan; 1982.

    Book  Google Scholar 

  17. Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J. Molecular cell biology. 4th ed. New York: W.H.Freeman; 2000.

    Google Scholar 

  18. Goodenough DA, Paul DL. Gap junctions. Cold Spring Harb Perspect Biol. 2009;1(1):002576. https://doi.org/10.1101/cshperspect.a002576.

    Article  Google Scholar 

  19. Rodríguez-Hernández CO, et al. Cell culture: history, development and prospects. Int J Curr Res Acad Rev. 2014;2(12):188–200.

    Google Scholar 

  20. Kasper C, Charwat V, Lavrentieva A. Cell culture technology. Cham: Springer; 2018.

    Book  Google Scholar 

  21. Amstein CF, Hartman PA. Adaptation of plastic surfaces for tissue culture by glow discharge. J Clin Microbiol. 1975;2(1):46–54.

    Article  CAS  Google Scholar 

  22. Ladoux B, et al. Strength dependence of cadherin-mediated adhesions. Biophys J. 2010;98(4):534–42. https://doi.org/10.1016/j.bpj.2009.10.044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Evans N, et al. Substrate stiffness affects early differentiation events in embryonic stem cells. Eur Cell Mater. 2009;18:1–14. https://doi.org/10.22203/eCM.v018a01.

    Article  CAS  PubMed  Google Scholar 

  24. Zustiak S, Nossal R, Sackett DL. Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs. Biotechnol Bioeng. 2014;111(2):396–403. https://doi.org/10.1002/bit.25097.

    Article  CAS  PubMed  Google Scholar 

  25. Discher DE. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;310(5751):1139–43. https://doi.org/10.1126/science.1116995.

    Article  CAS  PubMed  Google Scholar 

  26. Baker BM, Chen CS. Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues. J Cell Sci. 2012;125(13):3015–24. https://doi.org/10.1242/jcs.079509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mao AS, Shin J-W, Mooney DJ. Effects of substrate stiffness and cell-cell contact on mesenchymal stem cell differentiation. Biomaterials. 2016;98:184–91. https://doi.org/10.1016/j.biomaterials.2016.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Meyers J, Craig J, Odde DJ. Potential for control of signaling pathways via cell size and shape. Curr Biol. 2006;16(17):1685–93. https://doi.org/10.1016/j.cub.2006.07.056.

    Article  CAS  PubMed  Google Scholar 

  29. Ishii I. Histological and functional analysis of vascular smooth muscle cells in a novel culture system with honeycomb-like structure. Atherosclerosis. 2001;158(2):377–84. https://doi.org/10.1016/S0021-9150(01)00461-0.

    Article  CAS  PubMed  Google Scholar 

  30. McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6(4):483–95. https://doi.org/10.1016/S1534-5807(04)00075-9.

    Article  CAS  PubMed  Google Scholar 

  31. Carrel A. A method for the physiological study of tissues in vitro. J Exp Med. 1923;38(4):407–18. https://doi.org/10.1084/jem.38.4.407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Keshaw H, Forbes A, Day RM. Release of angiogenic growth factors from cells encapsulated in alginate beads with bioactive glass. Biomaterials. 2005;26(19):4171–9. https://doi.org/10.1016/j.biomaterials.2004.10.021.

    Article  CAS  PubMed  Google Scholar 

  33. Breslin S, O’Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov Today. 2013;18(5–6):240–9. https://doi.org/10.1016/j.drudis.2012.10.003.

    Article  CAS  PubMed  Google Scholar 

  34. Elliott NT, Yuan F. A review of three-dimensional in vitro tissue models for drug discovery and transport studies. J Pharm Sci. 2011;100(1):59–74. https://doi.org/10.1002/jps.22257.

    Article  CAS  PubMed  Google Scholar 

  35. Ronaldson-Bouchard K, Vunjak-Novakovic G. Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell. 2018;22(3):310–24. https://doi.org/10.1016/j.stem.2018.02.011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Skardal A, Shupe T, Atala A. Organoid-on-a-chip and body-on-a-chip systems for drug screening and disease modeling. Drug Discov Today. 2016;21(9):1399–411. https://doi.org/10.1016/j.drudis.2016.07.003.

    Article  CAS  PubMed  Google Scholar 

  37. Bartz C, Meixner M, Giesemann P, Roël G, Bulwin G-C, Smink JJ. An ex vivo human cartilage repair model to evaluate the potency of a cartilage cell transplant. J Transl Med. 2016;14(1):317. https://doi.org/10.1186/s12967-016-1065-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Eschen C, et al. Clinical outcome is significantly better with spheroid-based autologous chondrocyte implantation manufactured with more stringent cell culture criteria. Osteoarthr Cartil Open. 2020;2(1):100033. https://doi.org/10.1016/j.ocarto.2020.100033.

    Article  Google Scholar 

  39. Kapałczyńska M, et al. 2D and 3D cell cultures – a comparison of different types of cancer cell cultures. Arch Med Sci. 2018;14(4):910–9. https://doi.org/10.5114/aoms.2016.63743.

    Article  PubMed  Google Scholar 

  40. Costa EC, Silva DN, Moreira AF, Correia IJ. Optical clearing methods: an overview of the techniques used for the imaging of 3D spheroids. Biotechnol Bioeng. 2019;116(10):2742–63. https://doi.org/10.1002/bit.27105.

    Article  CAS  PubMed  Google Scholar 

  41. Bonnier F, et al. Cell viability assessment using the Alamar blue assay: a comparison of 2D and 3D cell culture models. Toxicol In Vitro. 2015;29(1):124–31. https://doi.org/10.1016/j.tiv.2014.09.014.

    Article  CAS  PubMed  Google Scholar 

  42. Hook K. Stem cells and respiratory disease. Lancet Respir Med. 2017;5(3):178–9. https://doi.org/10.1016/S2213-2600(17)30056-5.

    Article  PubMed  Google Scholar 

  43. Rashidghamat E, et al. Phase I/II open-label trial of intravenous allogeneic mesenchymal stromal cell therapy in adults with recessive dystrophic epidermolysis bullosa. J Am Acad Dermatol. 2019;83:447. https://doi.org/10.1016/j.jaad.2019.11.038.

    Article  CAS  PubMed  Google Scholar 

  44. Frerich B, Lindemann N, Kurtz-Hoffmann J, Oertel K. In vitro model of a vascular stroma for the engineering of vascularized tissues. Int J Oral Maxillofac Surg. 2001;30(5):414–20. https://doi.org/10.1054/ijom.2001.0130.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dominik Egger .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Egger, D., Nebel, S. (2021). Introduction to 3D Cell Culture. In: Kasper, C., Egger, D., Lavrentieva, A. (eds) Basic Concepts on 3D Cell Culture . Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-030-66749-8_1

Download citation

Publish with us

Policies and ethics