Making a difference with microtissue
BILLERICA, Mass.—Under the auspices of a Small Business Innovation Research contract from the National Cancer Institute, Seahorse Bioscience and the Moffitt Cancer Center have announced that they will be collaborating on the development of a reproducible method of measuring the metabolism of 3D microtissue, one that can be used for high-throughput metabolic and preclinical toxicity screens.
This partnership will focus on non-small cell lung cancers (NSCLC), specifically their response to targeted and non-targeted chemotherapeutic agents. While 2D cell cultures grown as flat monolayers have been the norm in research, 3D cell cultures comprised of multiple cell types offer more physiologically relevant models for in-vitro assays, which in turn can offer more accurate prediction of in-vivo outcomes.
“Right now in the cancer community, the success rate of transitioning in-vitro test results into the clinic or even in-vivo testing is very small, and so there’s a real need for a better model that’s more predictive of these in-vivo outcomes. And there’s a lot of evidence out there that points to the microenvironmental factors that you get within 3D tissues are a big piece of why 2D biology is not as predictive,” says Andrew Neilson, chief technical officer for Seahorse Bioscience.
Dr. Robert J. Gillies, vice chair of radiology and director of Moffitt’s experimental imaging program, and Seahorse Bioscience have worked together for a number of years to metabolically profile 3D microtissue models.
“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,” Gillies commented in a statement. “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.”
“We fundamentally believe that metabolism plays a critical role in the pathology of all diseases, not just cancer. Specific to cancer, as a cell increases its metastatic potential, there are phenotypic shifts that take place that cause those tissues to have a propensity to consume more glucose or other substrates, and they basically use that as fuel to increase their growth rate and invade other spaces,” adds Neilson. “We fundamentally measure metabolic fluxes by measuring oxygen consumption and proton production, and what we want to understand is how different signaling events in the cell trigger changes in flux, so connecting the dot between metabolic signaling and metabolic flux. We use the metabolic flux as a readout.”
Seahorse Bioscience and Moffitt will seek to develop feasibility data to quantitatively evaluate the metabolic effects of various treatments on NSCLC in hopes of advancing personalized cancer treatment. The partners will work with optimized 3D cell cultures and cancer biopsy tissue, and Seahorse Bioscience’s Seahorse Xfe96 Extracellular Flux Analyzer and novel Xfe96 Spheroid Microplates, which provide functional metabolic measurements from 3D spheroids, will support the research.
“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,” Neilson noted. “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.”
Ultimately, he says, the hope would be to have a method of evaluating treatments with a 3D microtissue model that has clinical relevance, enabling technicians to evaluate patients’ individual tumors and optimize a patient-specific regimen for them.