Abstract:
Three dimensional (3D) neuronal cell culture models are complex in vitro systems that enable earlier neurite outgrowth and functional network formation compared with 2 D neuronal cultures These 3 D models provide an advanced platform for molecular and cellular analyses of neurological and neurodegenerative diseases relative to healthy conditions Native brain tissue exhibits a low elastic modulus ranging from 30 to 500 Pa depending on brain region and developmental stage, and we and others have shown that neuronal network formation is highest in ultrasoft hydrogels.
Here, thiolated hyaluronic acid (HA SH) was crosslinked with two PEG linkers Hyaluronic acid, a major component of the brain extracellular matrix, was reinforced with triangular pore frames composed of poly(ɛ caprolactone)caprolactone)( fibres fabricated by melt electro–writing (Laminin, fibronectin, and collagen IV were added for ECM supplementation The 3D brain disease model comprises neurons, astrocytes, and glioma cells Astrocytes support neuronal growth and maturation by secreting growth factors into the extracellular matrix Neuron tumor cell interactions involving glioblastoma U 87 and breast tumor cells MDA MB 231 and MDA MB 361 were confirmed by expression of glutamate receptors (GluA 2 and vesicular glutamate transporter 1 (vGLUT 1 Electron microscopy indicated that these interactions closely resemble functional synapses, while astrocyte glioma interactions were positive for connexin 43.
Cell–cell communication is essential for functional network formation Calcium imaging revealed significantly increased and synchronized neuronal activity when neurons
were cultured in the presence of tumor cells Thus, the 3D MEW frame HA SH composite containing neurons, astrocytes, and tumor cells represents a ready to use model to study brain tumor resistance to therapies through combined drug application.
Bio:
Since 2012 Carmen Villmann is a full Professor of Molecular Neurobiology at the University Hospital Würzburg, Germany She is a biologist by training and studied at
Universities in Berlin, Hannover, both Germany and Boston, US During her PhD and Postdoc career, she submerged into neurobiology working on balances in neurotransmission between excitation and inhibition and their disturbances associated with various kinds of neurological disorders Recently, she also started to use 3D cellular models to better simulate diseases of the brain such as tumors which represent a suitable tool to better translate molecular findings towards clinical applications
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