More than 92% of drug candidates for Central Nervous System diseases fail in clinical trials. HCS Pharma has developed human 3D cellular model including the matricial microenvironment, in the aim to better select drug candidates. This model is available for High Content Screening on our Robotic Platform.
3D Phenotypic screening of neuroprotective molecules against Parkinson’s disease
Context: Parkinson’s Disease (PD) affects more than 10 million people worldwide. This disease is mainly characterized by movement symptoms, cause by the death of dopaminergic neurons. This neuronal death degeneration involved the microenvironment. Indeed, the Extracellular Matrix (ECM) is an essential element in cellular functions and is highly modified and involved in neurodegenerative mechanisms, including, the proteinopathy and the glial cell mediated-neuroinflammation. Therefore, it is important to include these elements in in vitro models to fully reproduce the disease and not missing some pathological pathways involving ECM elements.
HCS Pharma solution: 3D phenotypic screening in BIOMIMESYS® Brain, an organ-specific matrix which reproduce the brain ECM
BIOMIMESYS® Brain hydroscaffold™ is a hyaluronic acid-based matrix, grafted with structural and adhesion molecules, which mimics the cerebral extracellular matrix. It allows to culture cells in 3D in a relevant microenvironnement. In this matrix, dopaminergic neuronal cell line (Luhmes cells) form clusters with neurites (β-3-tubulin), and express neuronal maturity marker (NeuN) and dopaminergic neuron marker (tyrosin hydroxylase):
PD can be induce in vitro using a PD inducer, such as 6-hydroxydopamine, rotenone, MMP+, glutamate, paraquat, and erastin. Moreover, the astrocytes’ influence on neuronal degeneration can be considered in a coculture of dopaminergic neurons and primary human astrocytes in 3D in BOMIMESYS® Brain.
These models are available in 96-well plates, compatible with immunostaining and with robotic platforms, and thus can be used for the High Content Screening of your molecules.
The service: we co-incubate your molecules of interest with a PD inducers on dopaminergic neurons in 3D in BIOMIMESYS®, in mono- or co-culture with astrocyte, to asses their protective effect (decrease on the neuronal mortality compared to the PD control by fluorescence microscopy and automatized image analysis.
Read-out: quantitative neuronal viability (DRAQ7/Hoechst staining), neuronal marker expression (β-tubulin, Tyrosine hydroxylase, NeuN, synaptophysin, etc.), astrocyte marker expression (GFAP, etc.)
If you want to know more about this assay, feel free to contact us!