Affiliation:
1. Center for Alternatives to Animal Testing (CAAT) Department of Environmental Health and Engineering Bloomberg School of Public Health Johns Hopkins University Baltimore MD 21205 USA
2. Clinical Research Unit of the Antonio Pedro Hospital Fluminense Federal University Niteroi 24033‐900 Brazil
3. Laboratory of Neural Regeneration and Function Neurobiology Department Biology Institute Fluminense Federal University Niteroi 24210‐201 Brazil
4. Department of Ophthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore MD 21287 USA
Abstract
AbstractBrain microphysiological systems (bMPS) recapitulate human brain cellular architecture and functionality more closely than traditional monolayer cultures and have become increasingly relevant for the study of neurological function in health and disease. Existing 3D brain models vary in reflecting the relative populations of different cell types present in the human brain. Most models consist mainly of neurons, while glial cells represent a smaller portion of the cell populations. Here, by means of a chemically defined glial‐enriched medium (GEM), an improved method to expand the population of astrocytes and oligodendrocytes without compromising neuronal differentiation in bMPS, is presented. An important finding is that astrocytes also change in morphology when cultured in GEM, more closely recapitulating primary culture astrocytes. GEM bMPS are electro‐chemically active and show different patterns of calcium staining and flux. Synaptic vesicles and terminals observed by electron microscopy are also present. No significant changes in neuronal differentiation are observed by gene expression, however, GEM enhanced neurite outgrowth and cell migration, and differentially modulated neuronal maturation in two different cell lines. These results have the potential to significantly improve functionality of bMPS for the study of neurological diseases and drug discovery, contributing to the unmet need for safe human models.
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