Terrasso et al. published a study about a neuroprotection assay on a 3D model in 2017. They developed a 3D co-culture of neurons and astrocytes by means of an agitation-based culture system. Then they evaluated the neuroprotection potential of 36 compounds in pre-incubation, co-incubation and post-incubation over an oxidative injury induced by tBHP, compared to an antioxidant, Idebenone (positive control). They assessed cell viability using Presto blue™, a non destructive method based on resazurin reduction to measure metabolic activity. Finally they performed semi-automation of the assay with success.
This study highlights some important characteristics of a relevant model for neuroprotection assay:
First, a complex model including several cellular types is necessary to take into account cell-cell interactions. The presence of astrocytes is important in a neuroprotection model because they impact the response to neurotoxic and neuroprotective compounds (Gupta et al. 2012). Moreover the 3D culture allows to better mimic tissue structure and cellular interactions than in a 2D model. Automation allows to screen a large number of compounds with a high thoughput and a low variability.
Other characteristics can be interesting for a relevant in vitro model, in particular the presence of an extracellular matrix (ECM) to include the microenvironment.
HCS Pharma is developing in vitro brain-like models including these features thanks to BIOMIESYS® Brain hydroscaffold: 3D model for High Content Screening including different cellular types like neurons and astrocytes, ECM and microenvironment for an efficient drug discovery!
Finally, the ability of drug candidates to reach the brain should also be considered. In this aim we are also developing a human blood-brain barrier model and microfluidic systems to mimic at best the different brain compartments.
Terrasso A.P., Silva A.C., Filipe A., Pedroso P., Ferreira A.L., Alves P.M., Brito C. (2017) Human neuron-astrocyte 3D co-culture-based assay for evaluation of neuroprotective compounds. Journal of Pharmacological and Toxicological Methods, 19(5):779-87.
Gupta K, Patani R, Baxter P, Serio A, Story D, Tsujita T, Hayes JD, Pedersen RA, Hardingham GE, Chandran S (2012). Human embryonic stem cell derived astrocytes mediate non-cell-autonomous neuroprotection through endogenous and drug-induced mechanisms. Cell Death and Differentiation, 19(5), 779–87.