Toxicology in Music City

To start the meeting on the right note, Namandjé N. Bumpus, PhD, Chief Scientist for the US Food and Drug Administration (US FDA), delivered the Opening Plenary presentation. Dr. Bumpus shared how the use of single cell proteomics can increase our understanding of the mechanisms of xenobiotic-induced toxicity. Another important point in the presentation was how insight into cellular heterogeneity might be incorporated preclinically to strengthen the development and utility of model systems. 

The major spotlight of this year’s SOT was the response to the recent U.S. Food and Drug Administration (FDA) Modernization Act 2.0 signed on December 29, 2022. The bill essentially refutes the Federal Food, Drug, and Cosmetics Act of 1938, which mandated animal testing for every new drug development protocol. In other words, the FDA no longer requires new drugs to be tested in animals before being approved.

Considering the FDA Modernization Act 2.0, there was much greater attention to New Approach Methods (NAMs), toxicology assessments using microphysiological systems (MPS), and prediction of toxicology outcomes using Artificial Intelligence (AI) throughout the meeting. NAMs are needed to address the limitations of animal testing, such as the underlying physiological mechanisms that cannot be seen that are impacted by a substance. Moving away from animal models would also reduce costs and save time, allowing for additional chemical or substance safety testing. 

One NAM highlighted during the meeting was the use of Caenorhabditis elegans, which is a tiny roundworm that can be used in chemical hazard testing to help flag chemicals with the most potential for harm. This model eliminates the use of an animal model for a common toxicological assay. 

It was also noted that among the in vitro models performed for toxicology assays, an overwhelming majority of them were done using 3-D cultures, which includes spheroids, organoids, 3-D printed tissues, tissue on chips, microfluidics, transwell cultures, and other advanced in vitro models. Primary cell models were also emphasized as a means to reduce the use of animals in preclinical drug development. Overall, these in vitro models allow toxicologists to get closer to the physiological state of cells in vivo and generate biologically relevant data. 

ATCC’s Exhibitor Hosted Session

The use of primary and hTERT-immortalized cells was discussed at the ATCC Exhibitor-Hosted Session Primary and hTERT-Immortalized Cells: Physiologically Relevant Cell Models for Toxicological Assays. Although not an official part of the SOT Annual Meeting scientific program, its presentation was permitted by the Society.

Carolina Lucchesi, PhD, BioNexus Foundation Principal Scientist at ATCC, kicked off the presentation by discussing the modernization of ATCC’s portfolio, emphasizing our investment in key technologies to ensure ATCC products and services remain the definitive standards in biological research.

Next, Brian Shapiro, PhD, Marketing Segment Manager at ATCC, addressed the current toxicological models available at ATCC. He then provided a breakdown of each model type and indicated the optimal capabilities regarding in vivo characteristics, proliferative capacity, reproducibility, predictability, and ease of use. Overall, continuous cell lines are ideal for large screens early in the toxicological workflow as hTERT-immortalized primary cells display the physiological relevance of primary cells. The hTERT cells answer the need for a scalable source of in vivo-like cells, while primary cells are best implemented when donor diversity is needed.

The last portion of the session was delivered by Sujoy Lahiri, PhD, Lead Scientist at ATCC. This third verse showcased in-depth data on ATCC kidney, airway, and dermal models and their functionality. Here, Dr. Lahiri described how ATCC hTERT-immortalized solute transporter protein expressing RPTEC display many key characteristics that are lost when renal cells are removed from the in vivo situation. He also presented data on air-liquid interface (ALI) models built using primary human bronchial epithelial cells and hTERT-immortalized fibroblasts. The functionality of these models was evaluated to see the cytotoxic and inflammatory response to multiple toxicants; he observed that the models were shown to be consistent between different lots. Dr. Lahiri then closed with insights on epidermal models and how ALI models using primary or hTERT-immortalized human melanocytes, keratinocytes, and fibroblasts showed 3-D epidermal architecture and marker expression followed by the production of melanin from the melanocytes.

What ATCC can offer

Toxicologists are challenged to identify the adverse effects of a broad range of chemical/biological entities to protect people and the environment. It is critical that the standards and model organisms used in toxicological testing are reliable and authenticated. ATCC provides a symphony of renal, neural, airway, and skin cells as well as related media and reagents for applications like high-content imaging, high-throughput screening, 3-D culture, spheroid culture, permeability assays, metabolic stability and survival studies, transport activity measurement, and more.

These models and our functional testing further ATCC’s commitment to work in harmony with the toxicology community and the Society’s mission to create a safer and healthier world by advancing the science and increasing the impact of toxicology.

Did you know?

Did you know that ATCC provides multiple resources focused on toxicological applications, such as application notes, scientific posters, and webinars?