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Programming Microphysiological Systems for Children’s Health Protection
Citation:
Knudsen, T., B. Klieforth, AND W. Slikker. Programming Microphysiological Systems for Children’s Health Protection. Experimental Biology and Medicine. SAGE Publications, THOUSAND OAKS, CA, 242(16):1586-1592, (2017). https://doi.org/10.1177/1535370217717697
Impact/Purpose:
This commentary draws attention to progress being made with synthetic engineered in vitro systems that are human cell-based and intended to capture relevant biology and toxicology of microscale tissues and multi-organ circuits, and the opportunities and challenges for their application to alternative, more public health relevant and efficient chemical toxicity testing methods to evaluate developmental impacts of drug/chemical exposure.
Description:
Microphysiological systems (MPS) and computer simulation models that recapitulate the underlying biology and toxicology of critical developmental transitions are emerging tools for developmental effects assessment of drugs/chemicals. Opportunities and challenges exist for their application to alternative, more public health relevant and efficient chemical toxicity testing methods. This is especially pertinent to children’s health research and the evaluation of complex embryological and reproductive impacts of drug/chemical exposure. Scaling these technologies to higher throughput is a key challenge and drives the need for in silico models for quantitative prediction of developmental toxicity to inform safety assessments. One example is cellular agent-based models, constructed from extant embryology and produce data that may be used to simulate critical developmental transitions and thereby predict phenotypic consequences of disruption in silico. Biologically-inspired MPS models built from human iPS-derived cells and synthetic matrices to recapitulate organ-specific physiologies and native tissue architectures are providing exciting new research opportunities to advance the assessment of developmental toxicity and offer the possibility of deriving a full ‘human on a chip’ system, or a ‘Homunculus.’
