Since last year, our PhD student Véronique De Conto has been working on the impact of microenvironment in cerebral in vitro model.
- A cerebral in vitro model for neurotoxicity assessment: She compared many methods to differentiate SH-SY5Y cells in mature neuronal cells, in order to select a medium both effective and reproducible, in terms of cell proliferation stop and neurite elongation. She also tested the impact of coating on cell culture support. Then she characterized neuronal type obtained with the different methods. Finally, she compared cell sensitivity according to the differentiation method thanks to a library of compounds with known toxicity or control molecules. These works allowed to select a FBS-free media, which stopped cell proliferation, induced high neurite elongation, and high sensitivity. This model is now available in 96- and 384-well plates; it can be used to detect neurotoxicity of compounds, in particular in drug discovery but also in other fields!
- A cerebral in vitro model for neuroprotective molecule screening: in the frame of ferropotosis is an iron-dependent cell death pathway, recently demonstrated as involved in the dopaminergic neuron loss in Parkinson’s disease. In this context, Veronique has develop a model in 384 well plate based on dopaminergic neuron cell line, the Luhmes cells, treated by a ferroptosis inducer. This model has been already used for a screening of 1 280 molecules, which has been allow to find several potential neuroprotective molecules of interest for the central nervous system, in collaboration with the neurologist Pr. David Devos (Inserm U1171).
However, these models was bot in two dimensions. In the aim to develop more physiological cerebral in vitro models, Véronique and our senior scientist in biomaterials, Zied Souguir, has developed BIOMIMESYS® Brain, an acid hyaluronic based-hydroscaffold, which mimic the extracellular matrix. BIOMIMESYS® allows to cultivated cell in three dimensions in the matricial microenvironment. She tested several neuronal cell types in BIOMIMESYS® Brain, in particular the Luhmes cells, which form a neuronal network in the matrix, with a higher viability in BIOMIMESYS® Brain compare to classic 2D culture. Moreover, first tests showed that cells were less sensitive to Parkinson’s inducer in BIOMIMESYS® Brain, compare to 2D culture. These results showed an impact of the microenvironment on cell response, and they are interesting to develop a chronic model of Parkinson’s disease!
These results are very promising, and open many interesting prospects for this new thesis year!