Ask for high quality link by putting your email below

Please, double check your email!

Poster presented during the SLAS Building Biology in 3D symposium event in Cambridge on April, 20th 2023.

Title: 3D cell culture taking into account the extracellular matrix for bridging the gap between in vitro & in vivo: focus on cancer models

V. De Conto 1 *, M. Fernandes2, J. Cicero, V. Cheung 1, J. Leriche 1, M. Roudaut 1, A. Mogrovejo-Valdivia 1, E. Vandenhaute 1, Z. Kherrouche2 , R.A. Toillon, N. Maubon 1

 1 HCS pharma, 250 rue Salvador Allende, Biocentre Fleming Bâtiment A, 59120 Loos, France

 2  Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020 – UMR1277 – Canther – Cancer Heterogeneity, Plasticity and Resistance to Therapies, F-59000, Lille, France.

Abstract: In oncology, 97% of drug candidate fail in clinical trials. That highlights a lake of relevance of preclinical models used upstream to select therapeutic molecules. Indeed, human in vitro models don’t take into account the microenvironment of the cancerous cells, in particular the Extracellular Matrix (ECM). However, more and more studies demonstrate that both the composition and the stiffness of the ECM are modified in tumors and are strongly linked to cancer initiation, progression, and propagation, as well as in drug resistance. BIOMIMESYS® is a hyaluronic acid-based matrix bio-functionalized with structural and adhesion molecules of the ECM, which forms a relevant microenvironment for in vitro 3-dimensional cell culture. This ECM-like hydroscaffold™ combines both the advantages of solid scaffold (porosity and structure maintenance) and of hydrogels (cell-matrix interactions). This matrix is chemically defined, translucent and provided ready-to-used in multi-well plate format (96 and 384 well plates). It can be therefore used for High Content Screening. Moreover, its composition, porosity and stiffness can be modified, in the aim to reproduce the organ-specificity of the native ECM, or to mimic a pathological microenvironment like in cancer. Cancer cells can be advantageously grown in BIOMIMESYS® for several weeks in multi-well plates and in microfluidic chips for more advanced models. We observed that modifications in the matrix composition and stiffness modify the cell behavior. Moreover, we have demonstrated that the exposition of colon cancer cells cultured in BIOMIMESYS® Oncology matrix to an anti-proliferative drug showed a closer in vitro/in vivo correlation in the EC50 curve compared to 2D culture. In addition, thanks to collaborations with academic laboratories, we demonstrated that BIOMIMESYS® allows to reproduce in vitro the behavior of cancerous cells in vivo, like mutation effects and metastasis propagation, and could be a relevant alternative to animal models. These results showed that the matricial microenvironment modifies the behavior of cancerous cells in vitro and should be considered carefully both in fundamental research and in drug discovery. BIOMIMESYS® hydroscaffold™ offers a good in vitro/in vivo correlation, and is adapted to High Content Screening; it represents a powerful tool to better select drug candidate in preclinical trials and to increase the success rate in clinical trials.


Leave a Reply

This site uses Akismet to reduce spam. Learn how your comment data is processed.