Authors Siddiqui, T. ; Celikkaya, H. ; Atasavum, Z.T. ; Popova, S. ; Freudenberg, U. ; Werner, C. ; Kizil, C.
Title Three-dimensional biohybrid starPEG-heparin hydrogel cultures for modeling human neuronal development and Alzheimer´s disease pathology
Alzheimer´s Disease
Date 30.11.2022
Number 61118
Abstract In this chapter, we present the methodology currently used in our laboratory to generate a starPEG-MMP (starPEG)- and heparin maleimide HM06 (heparin)-based 3D cell culture system, in a hydrogel, that can be used to study human neuronal development and Alzheimer’s disease (AD) pathology. A 3D cell culture system can mimic the in vivo cellular environment better than a 2D format, in which these cells exhibit neural network formation, electrophysiological activity, tissue-specific extracellular matrix (ECM) deposition, and neurotransmitter responsiveness. When treated with amyloid beta-42 (Aß42) peptides, this system recapitulates many of the pathological effects of AD, including reduced neural stem cell proliferation, impaired neuronal network formation, dystrophic axonal ends, synaptic loss, failure to deposit ECM, elevated tau hyperphosphorylation, and formation of neurofibrillary tangles. Culturing human primary cortical astrocyte (pHA)- or induced pluripotent stem cell (iPSC)-derived human neural stem cells in this biohybrid hydrogel system has led to the discovery of novel regulatory pathways underlying neurodegenerative pathology in different phases of AD. <br />ISBN 978-1-0716-2655-9
Publisher Humana Press
Citation Humana Press (2022) 159-170

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