3D Cell Culture as a Model of Small Cell Lung Cancer Brain Metastasis
Amanda Linkous Ph.D., scientific center manager for the NCI Center for Cancer Systems at Vanderbilt, spoke about the value of 3D cell culture for research into the biology of small cell lung cancer (SCLC). More than half of SCLC patients develop brain metastases, with a lower than five percent, five-year survival rate. SCLC is extremely aggressive and heterogeneous, and seen in around 15 percent of all lung cancers.
Studying SCLC metastasis has previously required in vivo mouse models, and while they're living, they don't provide the same "human" microenvironment for tumor invasion. Moreover, tumor implantation usually takes around three to six months to progress.
Human cerebral organoids support a number of SCLC tumor cell lines, both neuroendocrine and non-neuroendocrine. These mini brains mimic the in vivo microenvironment, showing choroid plexus development and cortical layering. They also allow SCLC tumor cell proliferation and maintain tumor heterogeneity and phenotype as found in patients. The mini brains support invasion and growth, so they're ideal for studying not only oncogenesis, but also the response to chemotherapeutic drugs.
These are also easily scalable, so researchers can create hundreds of them from stem cells for screening large numbers of drug combinations, concentrations, and time points. High throughput screening and imaging studies show tumor cell volumes within each 3D cell culture for characterizing the response.
Key Takeaways: Mini brains provide a 'normal' human microenvironment in which to study SCLC tumor growth and invasion. These cerebral 3D cultures support a shortened tumor latency with distinct invasion patterns maintained, which offers a faster in vitro alternative to in vivo mouse brain implantation testing.
Corning® Matribot® Bioprinter Printed Domes for Organoid Drug Testing
Hilary Sherman, senior scientist at Corning Life Sciences who works extensively with 3D cell culture applications, demonstrated how the Corning Matribot bioprinter could streamline the workflow for consistency and reproducibility.
Using a pancreatic cancer PDO assay as an example, Sherman explained how bioprinting could be a valuable in vitro tool in the drug development process. Best practices for creating a PDO assay with the Matribot bioprinter included key features of the instrument, such as programmable software and full automation.
Emphasizing accuracy for droplet and dome dispensing, Sherman showed how the bioprinter dispensed uniformly across a 96-well plate, leading to low variation between wells with a coefficient of variation below 15 percent. High throughput imaging could then easily assess 3D culture response to chemotherapeutics for highly reproducible results that could screen multiple drugs for the best choice in personalized therapeutics.
Key Takeaways: The Matribot bioprinter handles a wide variety of biological tissue and cell culture materials. The ability to program delivery means that bioprinting is highly reproducible across many tissue culture vessels. Uniform dispensing with low variability from well to well means that PDO assay data is both valid and sensitive to drug-dependent responses.