High-throughput in vitro models lack human-relevant complexity, which undermines their ability to accurately mimic in vivo biologic and pathologic responses. The emergence of microphysiological systems (MPS) presents an opportunity to revolutionize in vitro modeling for both basic biomedical research and applied drug discovery. The MPS platform has been an area of interdisciplinary collaboration to develop new, predictive, and reliable in vitro methods for regulatory acceptance. The current MPS models have been developed to recapitulate an organ or tissue on a smaller scale. However, the complexity of these models (ie, including all cell types present in the in vivo tissue) with appropriate structural, functional, and biochemical attributes are often not fully characterized. Here, we provide an overview of the capabilities and limitations of the microfluidic MPS model (aka organs-on-chips) within the scope of drug development. We recommend the engagement of pathologists early in the MPS design, characterization, and validation phases, because this will enable development of more robust and comprehensive MPS models that can accurately replicate normal biology and pathophysiology and hence be more predictive of human responses.
Keywords: alternative; biomarker; cell culture techniques; drug development; in vitro; induced pluripotent stem cells; microphysiological system; model; organ on a chip; safety assessment.