Thomas R. Cox, Dec 2017
Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology
Our new paper on alternative collagen sources for 3D organotypic cultures for use as pre-clinical models is now out in Scientific Reports
Cellular interactions with the extracellular matrix (ECM) occur in a three-dimensional (3D) context and this essential aspect of the tumour microenvironment can lead to altered sensitivity to therapeutics and even act as a barrier to their delivery. This key feature is often overlooked in pre-clinical studies and is likely one of the central factors contributing to the high attrition rates of lead compounds within the pharmaceutical industry. This organotypic platform allows assessment of lead compounds in both the stromal compartment or in a 3D co-culture setting using large scale collagen preparations from alternative sources.
Organotypic co-cultures bridge the gap between standard two-dimensional culture and mouse models. Such assays increase the fidelity of pre-clinical studies, to better inform lead compound development and address the increasing attrition rates of lead compounds within the pharmaceutical industry, which are often a result of screening in less faithful two-dimensional models. Using large-scale acid-extraction techniques, we demonstrate a step-by-step process to isolate collagen I from commercially available animal byproducts. Using the well-established rat tail tendon collagen as a benchmark, we apply our novel kangaroo tail tendon collagen as an alternative collagen source for our screening-ready three-dimensional organotypic co-culture platform. Both collagen sources showed equal applicability for invasive, proliferative or survival assessment of well-established cancer models and clinically relevant patient-derived cancer cell lines. Additional readouts were also demonstrated when comparing these alternative collagen sources for stromal contributions to stiffness, organization and ultrastructure via atomic force microscopy, second harmonic generation imaging and scanning electron microscopy, among other vital biological readouts, where only minor differences were found between the preparations. Organotypic co-cultures represent an easy, affordable and scalable model to investigate drug responses within a physiologically relevant 3D platform.
Conway JRW et al. Three-dimensional organotypic matrices from alternative collagen sources as pre-clinical models for cell biology
Scientific Reports (2017) | doi: 10.1038/s41598-017-17177-5
Cancer Models, Extracellular Matrix
This work was supported by an NHMRC project grant, an NHMRC New Investigator Grant (APP1129766), an NBCF Innovator Grant, an ARC Future grant, a Len Ainsworth Pancreatic Cancer Fellowship, Cancer Council NSW grant, a Tour de Cure grant, a Sydney Catalyst scholarship, a CINSW fellowship (13/CDF1-01), a Philip Hemstritch Fellowship in Pancreatic Cancer, a Cancer Australia grant (APP1100722) and CRUK core funding.