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3D biocomposite culture enhances differentiation of dopamine-like neurons from SH-SY5Y cells: A model for studying Parkinson's disease phenotypes.

Authors :
Fiore NJ
Tamer-Mahoney JD
Beheshti A
Nieland TJF
Kaplan DL
Source :
Biomaterials [Biomaterials] 2022 Nov; Vol. 290, pp. 121858. Date of Electronic Publication: 2022 Oct 12.
Publication Year :
2022

Abstract

Studies of underlying neurodegenerative processes in Parkinson's Disease (PD) have traditionally utilized cell cultures grown on two-dimensional (2D) surfaces. Biomimetic three-dimensional (3D) cell culture platforms have been developed to better emulate features of the brain's natural microenvironment. We here use our bioengineered brain-like tissue model, composed of a silk-hydrogel composite, to study the 3D microenvironment's contributions on the development and performance of dopaminergic-like neurons (DLNs). Compared with 2D culture, SH-SY5Y cells differentiated in 3D microenvironments were enriched for DLNs concomitant with a reduction in proliferative capacity during the neurodevelopmental process. Additionally, the 3D DLN cultures were more sensitive to oxidative stresses elicited by the PD-related neurotoxin 1-methyl-4-phenylpyridinium (MPP). MPP induced transcriptomic profile changes specific to 3D-differentiated DLN cultures, replicating the dysfunction of neuronal signaling pathways and mitochondrial dynamics implicated in PD. Overall, this physiologically-relevant 3D platform resembles a useful tool for studying dopamine neuron biology and interrogating molecular mechanisms underlying neurodegeneration in PD.<br />Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Kaplan reports financial support was provided by National Institutes of Health.<br /> (Copyright © 2022. Published by Elsevier Ltd.)

Details

Language :
English
ISSN :
1878-5905
Volume :
290
Database :
MEDLINE
Journal :
Biomaterials
Publication Type :
Academic Journal
Accession number :
36272218
Full Text :
https://doi.org/10.1016/j.biomaterials.2022.121858