Our project leader in in vitro pharmacology Veronique De Conto will be present to the Federation of European Neurosciences Societies (FENS) congress, from 9 to 13 July in Paris. She will present a poster about the importance of microenvironment in cerebral in vitro models for phenotypic screening, in the frame of Parkinson’s disease.
Date & Time: 12-07-2022, 14:00 – 17:30, Poster Session 06 – Section: Emerging Mechanisms in Parkinson’s Disease. Board number: S06-346
Aim: About 90% of drug-candidates failed in clinical trials, in particular in neurology, due to a lack of efficacy. That highlights a lack of relevance in preclinical models, including in vitro models, which do not take into account the microenvironment, composed by glial cells and the Extracellular Matrix (ECM). The objective was to study the influence of the microenvironment in cerebral in vitro models, in the frame of Parkinson’s Disease (PD).
Methods: First, we analyzed the influence of astrocytes on Luhmes cell sensitivity, a dopaminergic neuronal cell line, in 2D culture. Then, we developed a hyaluronic acid-based hydroscaffold for 3D cell culture, which mimics the ECM, and study the sensitivity of Luhmes cells in this model. Thirdly, we performed a co-culture of Luhmes cells and astrocytes in this matrix, to form a complex model including both the glial and the matricial microenvironments.
Results: We observed a protective effect of astrocytes in 2D culture. In the hydroscaffold, Luhmes cells displayed a lower sensitivity compared to 2D culture, that was explained by a partial retention of toxic molecules in the matrix, and differences in neuronal protein expression. In the co-culture, we observed spheroids containing both neurons and astrocytes.
Conclusions: This work highlighted that the microenvironment of neurons can modify the neuronal response in vitro, and should thus be considered carefully in academic research and in drug discovery. This model can be now used to study the microenvironment modifications in pathological conditions, and to develop innovative drugs targeting the microenvironment.
Veronique is looking forward to meet you to discuss about her works, brain diseases, in vitro models and the brain extracellular matrix (which is too often forgotten despite his important role in the health and disease!).
If you want more information about 3D cell models using BIOMIMESYS® matrix but can not attend the congress, feel free to contact us !
The poster will be also available as a PDF poster placed on the app.
Authors: Veronique De Conto1, Vaihere Cheung1, Natacha Perrin1, Gregory Maubon1, Zied Souguir1, Elodie Vandenhaute1, Vincent Berezowski2, Nathalie Maubon1
1HCS Pharma, 250 rue Salvador Allende, 59120 Loos. 2 Lille Neurosciences and Cognition, Université de Lille – Université d’Artois, INSERM U1172 – Troubles Cognitifs Dégénératifs et Vasculaires, Département de Pharmacologie Médicale, Faculté de Médecine – Pôle Recherche, 1, Place de Verdun, 59045 LILLE Cedex