Utilizing cues from developmental neurogenesis and gliogenesis for better in vitro brain models

With a globally ageing population, neurodegenerative disease poses an increasingly greater risk to health span, yet there are still no curative treatments. Efficient biomimetic modelling is the underlying target for improving preclinical-to-clinical translation of therapies, yet current techniques are poorly translated to clinical studies: animal models, 2D cell culture, as well as 3D spheroid and organoid cultures all have disadvantages which could be resolved by a tuneable, standardized approach. As such, 3D tissue engineered human models have huge potential, but even biomimetic, repeatable, translatable engineered tissues lack maturity in the neural networks created. Neurogenesis and gliogenesis are the processes by which new neurons and glia are created in vivo, mediated by architectural, cellular microenvironmental, and signalling cues which could be adopted in the engineering and synthesis of 3D neural models. This review will look at neurogenic and gliogenic cues and their engineered incorporation to overcome common shortcomings of in vitro 3D neural models-namely maturity, complexity, and reproducibility.