A biofidelic 3D culture model to study the development of brain cellular systems.
Little is known about how cells assemble as systems during corticogenesis to generate collective functions. We built a neurobiology platform that consists of fetal rat cerebral cortical cells grown within 3D silk scaffolds (SF). Ivermectin (Ivm), a glycine receptor (GLR) agonist, was used to modulate cell resting membrane potential (Vmem) according to methods described in a previous work that implicated Ivm in the arrangement and connectivity of cortical cell assemblies. The cells developed into distinct populations of neuroglial stem/progenitor cells, mature neurons or epithelial-mesenchymal cells. Importantly, the synchronized electrical activity in the newly developed cortical assemblies could be recorded as local field potential (LFP) measurements. This study therefore describes the first example of the development of a biologically relevant cortical plate assembly outside of the body. This model provides i) a preclinical basis for engineering cerebral cortex tissue autografts and ii) a biofidelic 3D culture model for investigating biologically relevant processes during the functional development of cerebral cortical cellular systems.
Tufts University, Department of Biomedical Engineering, 4 Colby St., Medford, Massachusetts 02155, USA.
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Ren
Tufts University, Department of Biomedical Engineering, 4 Colby St., Medford, Massachusetts 02155, USA.
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Tufts University, Department of Biomedical Engineering, 4 Colby St., Medford, Massachusetts 02155, USA.|Austrian Centre of Industrial Biotechnology Konrad Lorenz Strasse 20, A-3430, Tulln, Austria.
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Herrero Acero
Tufts University, Department of Biomedical Engineering, 4 Colby St., Medford, Massachusetts 02155, USA.|Department of Pediatrics, Connecticut Children's Medical Center &UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030, USA.
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Tang-Schomer
Tufts University, Department of Biomedical Engineering, 4 Colby St., Medford, Massachusetts 02155, USA.|Department of Biology, Tufts University, 200 Boston Avenue, Suite 4600, Medford, Massachusetts 02155, USA.
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Özkucur
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000254:growth & development*; D005333:Fetus / Q000166:cytology; D007559:Ivermectin / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D007559:Ivermectin