Recreating Organ-Specific Tumor Environments In Vitro

The majority of deaths from cancer are caused by its spread to distant tissues and organs, a process known as metastasis.

Studying the molecular mechanisms underlying metastasis often relies on the use of a large number of animal models, principally mice, through in vivo studies. The landscape of medical research is changing, however, with a push towards reducing and refining the use of animals in research. Alternative models are needed to help address important research questions.

One such alternative is the use of organ-specific matrices for 3D cell culture. This technology replicates the microenvironments of key organs, such as the liver and brain, to reproduce cancer metastases in vitro similar to those observed in vivo.

At ELRIG’s Research & Innovation 2024 event, Technology Networks spoke to Dr. Véronique De Conto, project leader in in vitro pharmacology at HCS Pharma, to learn more about their powerful tools for in vitro metastasis propagation.

Molly Campbell (MC): HCS Pharma is a biotechnology company focused on in vitro research and development, specializing in high content screening (HCS) on 3D models. For readers who are unfamiliar, can you explain the importance of HCS?

Véronique De Conto (VDC): Phenotypic screening involves testing new drugs on cells, as opposed to target-based screening, which tests compounds against a specific molecular target. HCS is a sub-type of phenotypic screening, in which numerous parameters are analyzed simultaneously. The advantage of phenotypic screening and HCS is that it considers all cellular mechanisms as a whole, taking into account alternative and compensatory mechanisms. It is particularly interesting for complex and multifactorial diseases such as cancer.

MC: What are the key challenges HCS that scientists currently face?

VDC: The main challenge that scientists currently face in HCS is the use of relevant models. Indeed, in vitro models have been simplified for large-scale use. However, this simplification led to a lack of relevance and poor predictability, as shown by the dramatic failure rate in clinical trials: 90% of drug candidates fail in clinical trials, due to efficacy and safety issues. Therefore, scientists need relevant in vitro models to better select drug candidates from the earliest stages of drug discovery. Among the missing pieces, the extracellular matrix (ECM) is not considered in in vitro models, despite more and more studies demonstrating that it is involved in all physiological and pathological processes.

MC: Can you discuss the HCS Pharma product portfolio, and how these products aim to address these challenges?

VDC: To meet this need, HCS Pharma has developed BIOMIMESYS®, an innovative hyaluronic acid-based matrix biofunctionalized with structural and adhesion molecules of the human ECM, which provides a relevant microenvironment for in vitro 3D cell culture. This unique ECM-like hydroscaffold™ combines the advantages of both solid scaffolds (i.e., porosity and structure maintenance) and hydrogels (i.e., cell–matrix interactions), to fully reproduce the native ECM architecture. This matrix is chemically defined, translucent and provided ready-to-use in a multi-well plate format. It can be therefore used for HCS. Moreover, its composition and stiffness can be modified to reproduce the organ specificity of the native ECM, including brain, liver and adipose tissue matrices as first products already developed. These are the first organ-specific matrices on the market available for large-scale use.

We have also developed a pathological matrix reproducing the tumor ECM. These 3D cell culture matrices are available for sale, and we also offer personalized support to help our partners and customers to implement BIOMIMESYS® in their cell culture laboratories. We also offer phenotypic screening using the BIOMIMESYS® matrix as a service to take full advantage of our expertise in 3D cell culture.

MC: Are there any recent publications that outline the use of BIOMIMESYS® that you think are particularly exciting, and that you wish to highlight?

VDC: Thanks to numerous academic labs, several articles have been published as a proof-of-concept that BIOMIMESYS® is a promising tool to fill the gap between in vitro and in vivo.

Among them, an article about breast cancer metastasis development was published in Experimental Hematology & Oncology in December 2023. This article highlights the importance of ECM organ specificity in breast cancer metastasis behavior. In this context, BIOMIMESYS® Brain and BIOMIMESYS® Liver matrices – which differ in both composition and stiffness to fully reproduce the organ microenvironment – have made it possible to reproduce in vitro brain and liver metastasis behavior similar to that observed in mice. These results demonstrated that BIOMIMESYS® represents a powerful tool to study in vitro metastasis propagation, as well as an interesting alternative to animal testing.

More recently, an article about iPSC-derived liver organoids in BIOMIMESYS® was published in Bioengineering & Translational Medicine. In this study, the authors succeeded in obtaining liver organoids from iPSC in BIOMIMESYS®, containing all the cell types found in the liver, which were fully mature, functional and structurally organized.

Another article, published in Toxicology, demonstrated that BIOMIMESYS® matrix is also suitable for microfluidic chips.

MC: Can you discuss the importance of reducing animal testing in pharmaceutical, nutraceutical and cosmetic companies?

VDC: Animal testing presents ethical and scientific issues. In Europe, animal testing is prohibited for cosmetic assessment, but it is still mandatory for drug assessment, in particular for toxicological tests. However, there are inter-species differences that explain the high failure rate of drug candidates in clinical trials. Taken together with growing public awareness of animal suffering, it is necessary to offer alternative methods for drug and cosmetic assessment, but not at the expense of human health. Therefore, the development of predictive human in vitro models is crucial.

MC: What are the greatest challenges that you face as a start-up in the drug discovery space, and what could help/is helping you to overcome these challenges?

VDC: The biggest challenge is finding funding. Health issues require long-term research and development and can be cost-effective in the short term. Although we have a strong collaboration with academic researchers leading a growing number of proof-of-concepts, we still are looking for funding and strong partnerships that will help us improve the drug discovery process and human care.

BIOMIMESYS® is a versatile tool that must be developed. In the future, it could be used not only in multi-well plates for drug assessment, but also in bioreactors for cell amplification and regenerative medicine. 

Dr. Véronique De Conto was speaking to Molly Campbell, Senior Science Writer for Technology Networks.

About the interviewee:

Véronique is a project leader in in vitro pharmacology at HCS Pharma. HCS Pharma is a biotechnology company focused on in vitro R&D, specializing in HCS, namely automated cell imaging, on 3D cellular models.