Systems for localized release to mimic paracrine cell communication in vitro

Paracrine cell communication plays a pivotal role for signal exchange between proximal cells in vivo. However, this localized, gradient type release of mediators at very low concentrations (pg/ml), relevant during physiological and pathological processes, is rarely reflected within in vitro approaches. This review gives an overview on state-of-the-art approaches, which transfer the paracrine cell-to-cell communication into in vitro cell culture model setups. The traditional methods like trans-well assays and more advanced microfluidic approaches are included. The review focusses on systems for localized release, mostly based on microparticles, which tightly mimic the paracrine interaction between single cells in 3D micro-environments. Approaches based on single microparticles, with the main focus on affinity-controlled storage and release of cytokines, are reviewed and their importance for understanding paracrine communication is highlighted. Various methods to study the cytokine release and their advantages and disadvantages are discussed. Basic principles of the release characteristics, like diffusion mechanisms, are quantitatively described, including the formation of resulting gradients around the local sources. In vitro cell experiments using such localized microparticle release systems in approaches to increase understanding of stem cell behavior within their niches and regulation of wound healing are highlighted as examples of successful localized release systems for mimicking paracrine cell communication.