Poster : BIOMIMESYS®, a ready-to-use ECM for Relevant Phenotypic Screening

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Poster presented during the ELRIG UK event in Cambridge on March, 29th and 30th 2023.

Title: An Extracellular Matrix-like hydroscaffold for 3D cell culture to bring the gap between in vitro & in vivo: focus on cancer models

V. De Conto ¹ *, M. Fernandes², V. Cheung ¹, J. Leriche ¹, M. Roudaut ¹, A. Mogrovejo-Valdivia ¹, E. Vandenhaute ¹, Z. Kherrouche² , N. Maubon¹

In oncology, 97% of drug candidates fail in clinical trials, pointing a lack of relevance of preclinical models. Indeed, human in vitro models don’t take into account the microenvironment, in particular the Extracellular Matrix (ECM), although it is modified in tumors and strongly linked to cancer initiation, progression, propagation, and drug resistance.

BIOMIMESYS® is a hyaluronic acid-based matrix bio-functionalized with structural and adhesion molecules of ECM, providing a relevant microenvironment for in vitro 3D cell culture. This ECM-like hydroscaffold combines the advantages of solid scaffolds (porosity, structure) and hydrogels (cell-matrix interactions). It is chemically defined and ready-to-used in multi-well plates, thus it can be used for High Content Screening (HCS). Moreover, its composition and stiffness can be modified to reproduce the organ-specificity of the ECM, or to mimic a pathological microenvironment like in cancer.

Cancer cells can be advantageously grown in BIOMIMESYS® for several weeks. The EC50 curve of cancer cells exposed to an anti-cancerous drug showed a closer in vitro/in vivo correlation in BIOMIMESYS® than in 2D. We also demonstrated that BIOMIMESYS® allows to reproduce in vitro the behavior of cancerous cells in vivo, like mutation effects and metastasis propagation. These results showed that the matricial microenvironment modifies the behavior of cancerous cells in vitro and should be considered carefully in drug discovery. This hydroscaffold offers a good predictability and is adapted to HCS; it represents a powerful tool to better select drug candidates and to increase the success rate in clinical trials.

 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.

Poster presented during the SLAS event in San Diego on the 27th and 28th of February 2023.

Title: BIOMIMESYS® Hydroscaffold, a ready-to-use organ-specific Extracellular Matrix for Relevant Phenotypic Screening

Dr. Nathalie Maubon*, Dr. Véronique De Conto, Dr. Méryl Roudaut, Dr Alejandra Mogrovejo – Valdivia, Julien Leriche, Vaihere Cheung and Dr Elodie Vandenhaute

Abstract

The extracellular matrix (ECM) is present in all tissues and is a master regulator of cellular behavior and phenotype: it influences the anchorage of the cells, acts as a migration barrier and track, signal reservoir, low-affinity co-receptor, signal presenter and is a source of biochemical forces. The ECM in each tissue/organ is characterized by a specific composition, and by biochemical and biophysical properties. Importantly, ECM features are modified in different types of disease, like cancers and fibrotic conditions. Given the importance of the matricial microenvironment in maintaining tissue homeostasis and proper intercellular communications, we aim at integrating the ECM parameter in in vitro models to better mimic the in vivo complexity.

For this purpose, we have developed 3D cellular models using BIOMIMESYS®, a patented green chemistry hydroscaffold™ for 3D cell culture. This matrix exhibits unique dual properties, unifying hydrogel and solid scaffold features in a single matrix. This highly reproducible matrix is suitable for long-term 3D cell culture. BIOMIMESYS® is based on Hyaluronic Acid (HA), a major component of the ECM, biofunctionalized with other ECM components (collagens, adhesion proteins or peptides) depending on the organ/tissue of interest. Moreover, the stiffness is also modulated to fit with the healthy or pathological ECM to reproduce (elastic modulus from 0.1 to 16 kPa).

In this poster, we will exemplify the importance of the matricial environment with the improvement of cell longevity and functionality and with successful differentiation of human pluripotent stem cells (hiPSCs) into mature and functional 3D liver organoids within BIOMIMESYS®. Moreover, we will present some results in oncology field and how we can model the tumoral ECM with a representative range of stiffnesses (1, 8 and 16 kPa) in vitro.

By better mimicking the ECM microenvironment, the next generation of 3D cell culture models should help to model in vivo complexity with more relevance, and therefore to discover new effective therapies against diseases like cancers. Our 3D in vitro models, by taking into account the matricial microenvironment, aim at highly improving phenotypic screening for a better prediction of human outcomes.

Keyword: Extra-Cellular Matrix, 3D cell culture, Phenotypic Screening, High Content Screening, HCS