Abstract
Organoids and microphysiological systems represent two current approaches to reproduce organ function in vitro. These systems can potentially provide unbiased assays of function which are needed to understand the mechanism of action of environmental toxins. Culture models that replicate organ function and interactions among cell types and tissues move beyond existing screens that target individual pathways and provide a means to assay context-dependent function. The current state of organoid cultures and microphysiological systems is reviewed and applications discussed. While few studies have examined environmental pollutants, studies with drugs demonstrate the power of these systems to assess toxicity as well as mechanism of action. Strengths and limitations of organoids and microphysiological systems are reviewed and challenges are identified to produce suitable high capacity functional assays.
Highlights
Animal toxicological studies provide important information about the effects of a range of drugs, toxins and pollutants
Recent advances in cell culture technology, stem cell biology, biomaterials, microfluidics and biosensors have been applied to the development of human organoids [11] and human microphysiological systems [12]
We review and compare human organoid and microphysiological systems, summarize their application in toxicity studies and discuss advances needed to be used in a predictive manner for toxicological studies of environmental pollutants
Summary
Animal toxicological studies provide important information about the effects of a range of drugs, toxins and pollutants. The signaling pathways and responses activated in response to drugs, toxins, or pollutants are often very dependent on the local environment, strongly affecting the manner in which a drug or environmental chemical affects the response [10] To address these limitations, recent advances in cell culture technology, stem cell biology, biomaterials, microfluidics and biosensors have been applied to the development of human organoids [11] and human microphysiological systems (or organs-on-a-chip) [12]. Advances in methods to produce differentiated cells and tissues from human pluripotent stem (hPS) cells or human induced pluripotent stem (iPS) cells, as well as transdifferentiation from one cell type to another offer new opportunities to develop in vitro disease models to study mechanisms and develop new therapies. We review and compare human organoid and microphysiological systems, summarize their application in toxicity studies and discuss advances needed to be used in a predictive manner for toxicological studies of environmental pollutants
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