A Novel Approach to Increase Glial Cell Populations in Brain Microphysiological Systems.

Autor: Morales Pantoja IE; 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., Ding L; 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., Leite PEC; Clinical Research Unit of the Antonio Pedro Hospital, Fluminense Federal University, Niteroi, 24033-900, Brazil., Marques SA; Laboratory of Neural Regeneration and Function, Neurobiology Department, Biology Institute, Fluminense Federal University, Niteroi, 24210-201, Brazil., Romero JC; 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., Alam El Din DM; 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., Zack DJ; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Chamling X; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Smirnova L; 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.
Jazyk: angličtina
Zdroj: Advanced biology [Adv Biol (Weinh)] 2024 Aug; Vol. 8 (8), pp. e2300198. Date of Electronic Publication: 2023 Dec 07.
DOI: 10.1002/adbi.202300198
Abstrakt: Brain 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.
(© 2023 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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