3D tissue models to bridge the gap between cell culture and tissue in assessing electroporation

Abstract

The vast majority of studies on drug delivery by electroporation have been performed in vitro on cell cultures in 2D (cell monolayers or cells in suspension) and in vivo in animal models. The results obtained are often inconsistent. Threedimensional tissue models of increasing complexity are starting to be used to study mechanisms of electrotransfer of cytotoxic molecules and nucleic acids in a tissue context in vitro. These 3D models include collagen gel, normal and/or tumor spheroids, as well as human tissue substitutes produced by tissue engineering. Three-dimensional culture systems allow researchers to address the concept of cell organization in 3D and to take into account dynamic interactions between distinct cell types and surrounding extracellular matrix. Thus, 3D tissue models mimic biological tissue better than classical cell culture. Besides, this approach is an efficient and ethical alternative to the use of laboratory animals. Moreover, cells can be isolated directly from a patient. This offers the possibility to adapt treatment planning to that person's biological characteristics, leading to a potentially more effective and better tolerated therapeutic approach. Understanding and mastering the mechanisms of drug delivery by electrotransfer at the tissue scale will enable the development of new strategies to increase transfer efficiency while avoiding damage to surrounding tissue. Finally, this knowledge of mechanisms at the tissue scale will open the door of clinical applications to gene therapy and DNA vaccination and will promote the development of innovative, effective, and personalized therapies.