For decades, animal testing has been used in science to elucidate complex biological pathways and phenomena. With time, it appeared that differences exist in animal models that have less human relevance, and therefore, the development of innovative models became essential. One such novel model includes three-dimensional reconstructed human tissues for toxicological testing. It started with models of skin and eyes, but it is gradually expanding and includes models of many organ types. The Workshop Session “Building the Toolbox: Three-Dimensional Tissue Constructs as Problem Solvers” during the 2022 SOT Annual Meeting and ToxExpo discussed the current state of three-dimensional tissue constructs research, highlighting opportunities and challenges of this technology to toxicology studies.
The first talk was presented by Dr. Allison Hilberer from the Institute of In Vitro Sciences Inc., who talked about reconstructed human epidermis tissue models (RhE) in assessing photosafety. Dr. Hilberer discussed the advantages of three-dimensional tissue reconstructs over the monolayer model and technical considerations to address specific testing needs. The talk discussed the practicality of RhE models in addressing hazards and risks of photosafety. While describing technical aspects and considerations for its use, the presentation highlighted a general testing outline, evaluation of new solvents for multi-dose studies, and the latest modifications in reconstructed human epidermis phototoxicity assay.
The next talk, delivered by Dr. Stefan Pfuhler from Procter and Gamble Company, focused on the development, standardization, and validation of the reconstructed human skin assays in measuring DNA damage. Since 3D tissue models offer more in vivo–like behavior for key parameters like cell viability, proliferation, gene, and protein expression, they are more suited for dermal toxicity testing confirmed by reconstructed skin comet assay and micronucleus assay. Dr. Pfuhler also discussed the metabolic competency of 3D skin models similar to human skin such as first-pass metabolism. The latter part of the talk discussed the reproducibility, transferability, robustness, and predictive capacity of these skin-based assays.
The third talk was presented by Dr. Cynthia Ryan from ToxTech Solutions LLC about SENS-IS assay. SENS-IS assay is a 3D reconstructed human epidermis model that measures the upregulation of genes when exposed to chemicals. The talk focused on the method of assay and its ability in predicting both hazard and potency and demonstrating high specificity, sensitivity, and accuracy. Dr. Ryan discussed the future directions and plans to use the assay in the testing of antimicrobial agrochemical compounds to meet the regulatory requirement. In addition, there will be an expansion of test concentrations, thus providing more quantitative potency prediction.
The other two talks, presented by Dr. Arno Gutleb from Luxembourg Institute of Science and Technology and Dr. Shaun McCullough from US EPA, focused on air-liquid interface (ALI) cultures offering an invaluable biological relevance in understanding the effects of chemical exposures in the respiratory tract. Both speakers talked about various available in vitro models based on physiological relevance. However, there are always certain advantages and limitations to in vitro models in terms of toxicological response, but as Dr McCullough said, the best way to make progress is to identify problems. At this moment, it is hard to say which in vitro models predict toxicity better or have more human physiological relevance, but a rule of thumb is that in vitro models should be as complex as is required but as simple as possible.
This blog was prepared by an SOT Reporter and represents the views of the author. SOT Reporters are SOT members who volunteer to write about sessions and events in which they participate during the SOT Annual Meeting and ToxExpo. SOT does not propose or endorse any position by posting this article. If you are interested in participating in the SOT Reporter program in the future, please email Giuliana Macaluso.
On-demand recordings of all Featured and Scientific Sessions delivered during the 2022 SOT Annual Meeting and ToxExpo will be available to meeting registrants in the SOT Event App and Online Planner after their conclusion, through July 31, 2022.
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