There is a 90% failure in clinical trials, due to efficacy and safety issues, which frequently concerns the central nervous system. That points a lack of relevance of preclinical models used upstream. In this frame, the aim of this study was to develop more relevant cerebral in vitro models, by including the matricial and cellular microenvironments, for drug discovery in Parkinson's disease. HD available on https://hcs-pharma.com/poster---importance-of-matricial-and-cellular-microenvironments-in-in-vitro-models-for-drug-discovery-in-parkinsons-disease/

1. Introduction
What is the extracellular matrix (ECM)?
Conclusion and perspectives
Importance of matricial and cellular microenvironments in
in vitro models for drug discovery in Parkinson’s disease
Results
What is BIOMIMESYS® hydroscaffold?
Hyaluronic acid grafted with other ECM components : Composition and
physico-chemical properties tailored to mimic the ECM of each organ.
BIOMIMESYS® Brain : HA, RGDS, Collagen IV, cationic polymer.
Elastic modulus 0.1 kPa.
References
The ECM has diverse and crucial
roles, in health and disease
For more information, go to : hcs-pharma.com or
scan this QR-code.
* : veronique.deconto@hcs-pharma.com
De Conto V. (Loos, France)1*, Cheung V. (Loos, France)1, Maubon G. (Loos, France)1, Souguir Z. (Loos, France)1, Maubon N. (Loos,
France)1, Vandenhaute E. (Loos, France)1, Bérézowski V. (Lille, France)2
1HCS Pharma, Loos, France ; 2Lille Neuroscience & Cognition, Univ. Lille, Inserm, CHU-Lille, Lille, France
• Low success rate in drug discovery :
90% of failure in clinical trials (safety and efficacy)
• The Central Nervous System is highly involved :
The presence of ECM and glial cells influenced the sensitivity of
dopaminergic neurons to PD inducers. We now aim at testing PD
inducers on the co-culture in 3D. This model represents a promising
tool for the study of complex and chronic diseases such as PD.
Goal : To improve the predictivity of in vitro models
• Taking into account the 3D cell organization
• Including the cellular and matricial microenvironments
Lack of relevance of preclinical models to select drug candidates
Cook et al. 2014
Brain ECM:
• 20% of cerebral volume
• Ratio GAG*/Collagen : 10/1
 Low stifness
Hydroscaffold
Hydrogels:
Biohydric medium
Cells encapsulated
Pathological or no relevant ECM
Solid Scaffolds:
Porous, No ECM
Decellularized organs
Complete ECM
Difficult tissue
access,
not
reproducible
Porous, physiological, reproducible.
• Impact of matrix on neuronal sensitivity • Co-culture of neuronal and glial cells
• Impact of astrocytes on neuronal sensitivity (2D)
Methods
The cells were less sensitive to PD* inducers in 3D that in 2D, that was
partially or totally explained by molecules retention in the matrix.
The PD inducers led to the activation of astrocytes (increase in GFAP
expression). However, the presence of astrocytes decreased the cell
sensitivity, probably link to their secretion properties which can
promote cell adhsesion or protect cells.
*GAG: Glycosaminoglycans
*PD: Parkinson’s disease
Cook, D., Brown, D., Alexander, R., March, R., Morgan, P., Satterthwaite, G., Pangalos, M.N., 2014. Lessons
learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat. Rev. Drug Discov. 13,
419–431. https://doi.org/10.1038/nrd4309
Illustration source : Biorender
Luhmes + erastin Coculture + erastin Luhmes Coculture
Scale bar = 200µm.
(Scanning electron microscope)
GFAP TUBB3