Opportunities and Challenges of Predictive Human in vitro Assay Development in a High Throughput Platform for Improving Translational Quality and Efficiency
Abstract: Complex in vitro models (CIVMs), also called microphysiological systems (MPS), are emerging tools to study cell-cell and cell-microenvironment interactions within a three-dimensional context and to better translate research findings to clinical studies as they faithfully recapitulate human physiology and pathology. With the advent of human induced pluripotent stem cell (iPSC) and iPSC derived cells, CIVMs enable extensive access to engineered human organotypic tissues for basic and translational research. Increasing level of throughput and physiological complexity of the system remains challenges in developing robust high-throughput (HT) assays. The 3D Tissue Bioprinting Laboratory (3D-TBL) at National Center for Advancing Translational Sciences (NCATS) tackles such roadblocks through multidisciplinary collaborations and implementing cutting-edge technologies, aiming to establish predictive human in vitro models with robust HT 3D assay readouts. Starting with establishing biofabricating protocols of outer blood retina barrier and skin tissue equivalents, 3D-TBL has successfully applied the protocols to various organ-specific tissue models and engineering platforms. Several technologies are being investigated to validate structure and function of biofabricated tissues, to develop HT-measurements, and to automate 3D assays. The presentation will cover the current progress of CIVM development at NCATS 3D-TBL and discuss the challenges in assay development and predictability assessment.