3D culture models to assess tissue responses to electroporation

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.