3D Culture Models to Assess Tissue Responses to Electroporation

Living reference work entry

Abstract

Cell and tissue responses to external stimuli are difficult to study in vivo. Traditional monolayer culture conditions allow for observation of cellular response to stimuli in vitro with a great degree of control and manipulation of experimental conditions; however, many studies have shown that cells exhibit different gene expression patterns, drug resistance, and mechanical stress responses in two-dimensional environments, than when cultured in three-dimensional (3D) culture environments or in vivo. Cell-cell and cell-matrix interactions determine many aspects of cellular behavior, including proliferation, metabolism, differentiation potential, and viability. Therefore, many biomimetic strategies exist for 3D cell culture for various applications. This chapter describes 3D culture methods for assessing tissue response to exogenous stimuli, specifically electroporation. These methods include spheroid culture, cell culture on electrospun scaffolds, and cell culture on decellularized human dermal matrices. Spheroid culture is generally recognized as a model system for tumor development and has been used extensively to study electroporation effects. Other 3D culture techniques include using electrospun scaffolds for various tissues such as oral mucosa and head and heck squamous carcinoma, and can be readily adapted to studying electroporation effects. Decellularized human dermis has been recently demonstrated as an excellent substrate for recapitulating human skin and used for electroporation applications.

Keywords

Electroporation Electrotransfer Gene therapy 3D cell culture Biomimicry Spheroid Extracellular matrix Electrospinning Cryogenic electrospinning 

References

  1. Barnes CP, Sell SA, Boland ED, Simpson DG, Bowlin GL (2007) Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev 59(14):1413CrossRefGoogle Scholar
  2. Blakeney B, Tambralli A, Anderson J et al (2011) Cell infiltration and growth in a low density, uncompressed three-dimensional electrospun nanofibrous scaffold. Biomaterials 32(6):1583CrossRefGoogle Scholar
  3. Brauker JH, Carr-Brendel VE, Martinson LA, Crudele J, Johnston WD, Johnson RC (1995) Neovascularization of synthetic membranes directed by membrane microarchitecture. J Biomed Mater Res 29(12):1517–1524CrossRefGoogle Scholar
  4. Bulysheva A, Bowlin G, Klingelhutz A, Yeudall WA (2012) Low-temperature electrospun silk scaffold for in vitro mucosal modeling. J Biomed Mater Res A 100(3):757–767CrossRefGoogle Scholar
  5. Bulysheva AA, Bowlin GL, Petrova SP, Yeudall WA (2013) Enhanced chemoresistance of squamous carcinoma cells grown in 3D cryogenic electrospun scaffolds. Biomed Mater 8(5):055009. doi:10.1088/1748-6041/8/5/055009CrossRefGoogle Scholar
  6. Bulysheva AA, Burcus N, Lundberg C, Edelblute CM, Francis MP, Heller R (2016) Recellularized human dermis for testing gene electrotransfer ex vivo. Biomed Mater 11(3):035002. doi:10.1088/1748-6041/11/3/035002CrossRefGoogle Scholar
  7. Canatella PJ, Black MM, Bonnichsen DM, McKenna C, Prausnitz MR (2004) Tissue electroporation: quantification and analysis of heterogeneous transport in multicellular environments. Biophys J 86(5):3260–3268. doi:10.1016/S0006-3495(04)74374-XCrossRefGoogle Scholar
  8. Chopinet L, Wasungu L, Rols MP (2012) First explanations for differences in electrotransfection efficiency in vitro and in vivo using spheroid model. Int J Pharm 423(1):7–15. doi:10.1016/j.ijpharm.2011.04.054CrossRefGoogle Scholar
  9. Frandsen SK, Gibot L, Madi M, Gehl J, Rols MP (2015) Calcium electroporation: Evidence for differential effects in normal and malignant cell lines, evaluated in a 3D spheroid model. PLoS One 10(12):e0144028. doi:10.1371/journal.pone.0144028CrossRefGoogle Scholar
  10. Freshney RI 2005 Culture of animal cells: a manual of basic technique, 5th edn. Wiley-Liss, Hoboken, p 642. http://www.loc.gov/catdir/enhancements/fy0626/2005281585-d.html; http://www.loc.gov/catdir/enhancements/fy0626/2005281585-b.html CrossRefGoogle Scholar
  11. Gibot L, Rols MP (2013) 3D spheroids’ sensitivity to electric field pulses depends on their size. J Membr Biol 246(10):745–750. doi:10.1007/s00232-013-9535-xCrossRefGoogle Scholar
  12. Gibot L, Wasungu L, Teissie J, Rols MP (2013) Antitumor drug delivery in multicellular spheroids by electropermeabilization. J Control Release 167(2):138–147. doi:10.1016/j.jconrel.2013.01.021CrossRefGoogle Scholar
  13. Griffith L, Swartz M (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7(3):211CrossRefGoogle Scholar
  14. Jin H, Chen J, Karageorgiou V, Altman G, Kaplan D (2004) Human bone marrow stromal cell responses on electrospun silk fibroin mats. Biomaterials 25(6):1039CrossRefGoogle Scholar
  15. Leong M, Rasheed M, Lim T, Chian K (2009) In vitro cell infiltration and in vivo cell infiltration and vascularization in a fibrous, highly porous poly(D,L-lactide) scaffold fabricated by cryogenic electrospinning technique. J Biomed Mater Res A 91(1):231–240CrossRefGoogle Scholar
  16. Leong M, Chan W, Chian K, Rasheed M, Anderson J (2010) Fabrication and in vitro and in vivo cell infiltration study of a bilayered cryogenic electrospun poly(D,L-lactide) scaffold. J Biomed Mater Res A 94(4):1141–1149Google Scholar
  17. Marrero B, Heller R (2012) The use of an in vitro 3D melanoma model to predict in vivo plasmid transfection using electroporation. Biomaterials 33(10):3036–3046. doi:10.1016/j.biomaterials.2011.12.049CrossRefGoogle Scholar
  18. Marrero B, Messina JL, Heller R (2009) Generation of a tumor spheroid in a microgravity environment as a 3D model of melanoma. In Vitro Cell Dev Biol Anim 45(9):523–534. doi:10.1007/s11626-009-9217-2CrossRefGoogle Scholar
  19. Mellor HR, Davies LA, Caspar H et al (2006) Optimising non-viral gene delivery in a tumour spheroid model. J Gene Med 8(9):1160–1170. doi:10.1002/jgm.947CrossRefGoogle Scholar
  20. Sheikh FA, Ju HW, Lee JM et al (2015) 3D electrospun silk fibroin nanofibers for fabrication of artificial skin. Nanomedicine 11(3):681–691. doi:10.1016/j.nano.2014.11.007CrossRefGoogle Scholar
  21. Simonet M, Schneider OD, Neuenschwander P, Stark WJ (2007) Ultraporous 3D polymer meshes by low-temperature electrospinning: use of ice crystals as a removable void template. Polym Eng Sci 47(12):2020–2026CrossRefGoogle Scholar
  22. Stankus JJ, Soletti L, Fujimoto K, Hong Y, Vorp DA, Wagner WR (2007) Fabrication of cell microintegrated blood vessel constructs through electrohydrodynamic atomization. Biomaterials 28(17):2738CrossRefGoogle Scholar
  23. Wasungu L, Escoffre JM, Valette A, Teissie J, Rols MP (2009) A 3D in vitro spheroid model as a way to study the mechanisms of electroporation. Int J Pharm 379(2):278–284. doi:10.1016/j.ijpharm.2009.03.035CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Frank Reidy Research Center for BioelectricsOld Dominion UniversityNorfolkUSA
  2. 2.School of Medical Diagnostics and Translational SciencesOld Dominion UniversityNorfolkUSA

Personalised recommendations