Three-Dimensional Environment Sustains Morphological Heterogeneity and Promotes Phenotypic Progression During Astrocyte Development

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dc.contributor.authorBalasubramanian, Swarnalatha
dc.contributor.authorPackard, John A.
dc.contributor.authorLeach, Jennie B.
dc.contributor.authorPowell, Elizabeth M.
dc.date.accessioned2018-12-17T15:46:43Z
dc.date.available2018-12-17T15:46:43Z
dc.date.issued2016-06-01
dc.description.abstractAstrocytes are critical for coordinating normal brain function by regulating brain metabolic homeostasis, synaptogenesis and neurotransmission, and blood–brain barrier permeability and maintenance. Dysregulation of normal astrocyte ontogeny contributes to neurodevelopmental and neurodegenerative disorders, epilepsies, and adverse responses to injury. To achieve these multiple essential roles, astrocyte phenotypes are regionally, morphologically, and functionally heterogeneous. Therefore, the best regenerative medicine strategies may require selective production of distinct astrocyte subpopulations at defined maturation levels. However, little is known about the mechanisms that direct astrocyte diversity or whether heterogeneity is represented in biomaterials. In vitro studies report lack of normal morphologies and overrepresentation of the glial scar type of reactive astrocyte morphology and expression of markers, questioning how well the in vitro astrocytes represent glia in vivo and whether in vitro tissue engineering methods are suitable for regenerative medicine applications. Our previous work with neurons suggests that the three-dimensional (3D) environment, when compared with standard two-dimensional (2D) substrate, yields cellular and molecular behaviors that more closely approximately normal ontogeny. To specifically study the effects of dimensionality, we used purified glial fibrillary acidic protein (GFAP)-expressing primary cerebral cortical astrocyte cultures from single pups and characterized the cellular maturation profiles in 2D and 3D milieu. We identified four morphological groups in vitro: round, bipolar, stellate, and putative perivascular. In the 3D hydrogel culture environment, postnatal astrocytes transitioned from a population of nearly all round cells and very few bipolar cells toward a population with significant fractions of round, stellate, and putative perivascular cells within a few days, following the in vivo ontogeny. In 2D, however, the population shift from round and bipolar to stellate and perivascular was rarely observed. The transition to distinct cellular morphologies in 3D corresponded to the in vivo expression of phenotypic markers, supporting the generation of mature heterogeneous glial populations in vitro. This study presents quantitative data supporting that 3D culture is critical for sustaining the heterogeneity of astrocytes in vitro and for generating a representation of the in vivo portfolio of heterogeneous populations of astrocytes required for therapeutic interventions in neurodevelopmental disorders, epilepsy, and brain injury.en_US
dc.description.sponsorshipThis work was supported by NIH-NINDS R01NS065205 (JBL and EMP) and a UMBC Undergraduate Research Award (JAP).en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913501/en_US
dc.format.extent14 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/M2K35MJ2F
dc.identifier.citationSwarnalatha Balasubramanian , John A. Packard, Jennie B. Leach , and Elizabeth M. Powell, Three-Dimensional Environment Sustains Morphological Heterogeneity and Promotes Phenotypic Progression During Astrocyte Development, Tissue Engineering Part A, Vol. 22, No. 11-12 , 2016, https://doi.org/10.1089/ten.tea.2016.0103en_US
dc.identifier.urihttps://doi.org/10.1089/ten.tea.2016.0103
dc.identifier.urihttp://hdl.handle.net/11603/12277
dc.language.isoen_USen_US
dc.publisherMary Ann Liebert, Incen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemical, Biochemical & Environmental Engineering Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.subjectthree-dimensionalen_US
dc.subjectmorphological heterogeneityen_US
dc.subjectastrocyte developmenten_US
dc.subjectphenotypicen_US
dc.subjectpurified glial fibrillary acidic protein (GFAP)-expressing primary cerebral cortical astrocyte cultures
dc.subjecttherapeutic interventions in neurodevelopmental disorders, epilepsy, and brain injury
dc.titleThree-Dimensional Environment Sustains Morphological Heterogeneity and Promotes Phenotypic Progression During Astrocyte Developmenten_US
dc.typeTexten_US

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