Thomas Meynard is a PhD student in OncoLille Laboratory (Canther Lab, Mucine Team), under the supervision of Dr. Isabelle Van Seuningen and Dr. Vincent Senez. His PhD work is focused on the development of microfluidic systems to study Pancreatic Ductal AdenoCarcinoma (PDAC). To reproduce the tumoral Extracellular Matrix (ECM), he includes BIOMIMESYS®hydroscaffold in his microfluidics devices. This summer, Thomas won the poster of the day prize at the FEBS 2023 congress for his poster entitled “Development of a 3D co-culture model within a microfluidic system to study pancreatic tumor–stroma interactions and drug resistance“, and he is also one of the 4 main winners of the FEBS 2023 Congress poster prize, out of a total of 652 posters. Congratulations Thomas!
Find below the summary:
Development of a 3D co-culture model within a microfluidic system to study pancreatic
tumor–stroma interactions and drug resistance
T. Meynard1, F. Royer1, S. Paget1,2, A. Mogrojevo Valdivia3,N. Maubon3, A. Vincent1,2, V. Senez1, I. Van Seuningen1
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality and is projected to become second by 2030. This cancer has a very poor prognosis as it is often detected at an advanced stage. In order to recreate PDAC, its main characteristics must be reproduced. This includes a dense stroma composed of a large population of fibroblasts that overexpress extracellular matrix (ECM) proteins. This stromal density favors increased tumor stiffness and intratumoral pressure impacting mass transport which in the end leads to chemoresistance. Therefore, our goal is to create a model that reproduces the physical characteristics of PDAC: interstitial flow, a biologically relevant culture matrix with varying levels of stiffness, and the application of different levels of compression. Our model
consists either in PDAC-derived tumoroids or in a co-culture of both human pancreatic cancer and activated stellate cells. The microenvironment is an ECM composed of hyaluronic acid and collagen I which stiffness is variable (1; 8; 16 kPa). The impact of stiffness on protein expression is studied by western blotting and immunofluorescence. Polydimethylsiloxane microfluidic chips are fabricated using a precision 3D printer. Our results show that our co-culture model recapitulates the expression of epithelial
(E-cadherin) and mesenchymal (Vimentin, a-SMA) markers, oncogenic signalling pathways (b-catenin, MAPK), and mechanobiological actors (YAP/TAZ). We now plan to integrate the biological model into our microfluidic system in order to precisely control the compression of the model and mass transport
to study chemoresistance. In conclusion, we have developed and characterized a parallelized microfluidic system allowing the compression of biological material. In parallel, we have established a relevant model of PDAC composed of a co-culture in a matrix with variable stiffness, which composition is optimized for fibroblast activation.
1 Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 – CANTHER – Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France. 2 ORGALille 3D organoid culture platform, OrgaRES core facility, CANTHER laboratory, F-59000 Lille, France, 3 HCS Pharma, Biocentre Fleming, 250 rue Salvador
Allende, Bat A, 59120 Loos, France
*The authors marked with an asterisk equally contributed to the work