[Toxicology in Vitro] Architecture in 3D cell culture: An essential feature for in vitro toxicology
Three-dimensional cell culture has the potential to revolutionize toxicology studies by allowing human-based reproduction of essential elements of organs. Beyond the study of toxicants on the most susceptible organs such as liver, kidney, skin, lung, gastrointestinal tract, testis, heart and brain, carcinogenesis research will also greatly benefit from 3D cell culture models representing any normal tissue. No tissue function can be suitably reproduced without the appropriate tissue architecture whether mimicking acini, ducts or tubes, sheets of cells or more complex cellular organizations like hepatic cords. In this review, we illustrate the fundamental characteristics of polarity that is an essential architectural feature of organs for which different 3D cell culture models are available for toxicology studies in vitro. The value of tissue polarity for the development of more accurate carcinogenesis studies is also exemplified, and the concept of using extracellular gradients of gaseous or chemical substances produced with microfluidics in 3D cell culture is discussed. Indeed such gradients-on-a-chip might bring unprecedented information to better determine permissible exposure levels. Finally, the impact of tissue architecture, established via cell-matrix interactions, on the cell nucleus is emphasized in light of the importance in toxicology of morphological and epigenetic alterations of this organelle.
Sophie A. Lelièvrea, b, c, , , Tim Kwokb, Shirisha Chittiboyinaa, b a Purdue University, Department of Basic Medical Sciences, 625 Harrison Street, West Lafayette, IN 47907, USA b 3D Cell Culture Core (3D3C) Facility, Birck Nanotechnology Center, Purdue University Discovery Park, 1205 West State Street, West Lafayette, IN 47907, USA c Purdue University Center for Cancer Research, 201 S University Street, West Lafayette, IN 47907, USA Received 30 December 2016, Revised 20 March 2017, Accepted 28 March 2017, Available online 30 March 2017 http://dx.doi.org/10.1016/j.tiv.2017.03.012