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Seahorse Bio, Moffitt to Develop Method for Measuring Metabolism of 3D Microtissue

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Seahorse Bioscience and the Moffitt Cancer Center have announced that they have received an SBIR contract through the National Cancer Institute, to develop a reproducible method that will enable the measurement of metabolism of 3D microtissue, and can be used for high-throughput metabolic and pre-clinical therapy and toxicity screens.

Cancer cells switch their metabolic pathways to survive. The ability to perform real time measurements of the metabolism of tumors will provide important information in developing anti-cancer drugs. The work will focus on the testing of non-small cell lung cancers (NSCLC), to investigate response to both targeted and non-targeted chemotherapeutic agents. Historically, research tools have focused on 2D cell cultures of cancer cells grown as flat monolayers. In contrast, 3D cell cultures that contain multiple cell types provide a more physiologically relevant model for in vitro assays, with the potential for better predictability of in vivo outcomes.

The goal of the study is to develop the feasibility data to quantitatively assess the metabolic effects of various treatments on NSCLC, with an ultimate aim of advancing personalized cancer treatment. The work will involve both optimized 3D cell cultures (spheroids), as well as cancer tissue procured via biopsy. Optimization will establish standard processing protocols to yield consistent micro-tissue samples, and then measuring the metabolic signatures of the samples in response to therapeutic treatments.

Robert J. Gillies, Ph.D., vice-chair of radiology and director of Moffitt’s experimental imaging program, has been working with Seahorse Bioscience for several years to metabolically profile 3D microtissue models, which hold promise to be more predictive in vivo. The research will be done using the Seahorse XFe96 Extracellular Flux Analyzer and novel XFe96 Spheroid Microplates, which provide functional metabolic measurements from 3D spheroids.

"This is a very exciting opportunity because we know that the metabolism of intact cancer tissue is complex, and involves cross-talk between the cancer cells and the supporting host cells," stated Dr. Gillies. "This metabolic syncytium is necessary for cancers to thrive, and itself presents opportunities for novel therapies that could not be assessed in monoculture. Also, we fully expect that the response of these complex tissues to current and novel therapeutics will be highly predictive of their behavior in a patient."

"Seahorse XF technology is proven for the measurement of metabolism in pancreatic islets, now we’re applying our knowledge to measuring spheroid metabolism. XF 3D metabolic assays have the potential to impact cancer research as we enable scientists to analyze a more in vivo model of cancer metabolism," stated Andrew Neilson, chief technical officer for Seahorse Bioscience. "These methods should allow us to evaluate the efficacy of a wide range of treatments using 3D microtissues. These XF assays can be applied to most tumor cell lines, enabling scientists to probe drug effects on metabolic pathways, and develop personalized therapies tailored to the tumor characteristics."

The potential for commercialization of an economical method to evaluate the efficacy of various therapeutic treatments using a 3D microtissue model holds great promise. The method, if successful, will be compatible with most tumor cell lines and will have the capability for co-culture with human primary cells. The long-term goal is to move into translational medicine, developing ways to characterize tumors using small tissue biopsies. Additionally, applications for XF 3D microtissue assay technology will extend beyond cancer to also include diabetes, obesity, toxicology, stem cell therapy and neurodegeneration research.