Issue 5, 2013

Synthetic hydrogel platform for three-dimensional culture of embryonic stem cell-derived motor neurons

Abstract

Culturing mammalian neurons in three-dimensional (3D) microenvironments that more closely recapitulate critical biochemical and biophysical aspects of the developing or adult central nervous system (CNS) milieu remains a significant challenge in neurobiological studies and in regenerative medicine. Here, we aimed to exploit recent advances in poly(ethylene glycol) (PEG) hydrogel chemistries to define a synthetic niche capable of supporting the culture and axonal outgrowth of both aggregated and dissociated mouse embryonic stem cell-derived motor neurons (ESMNs). Using thiol-ene click chemistry to create peptide crosslinked PEG hydrogels, we identified a hydrogel formulation that promotes neuronal survival and axon outgrowth through cell–extracellular matrix interactions, such as those between the laminin-derived peptide YIGSR and its integrin, and that allows neurons to remodel their extracellular environment through matrix metalloproteinase (MMP)-mediated polymer network degradation. Our results demonstrate a 3D platform for culture of both aggregated and single mammalian motor nerve cells that not only permits cell survival over more than a week of culture, but also allows for the robust extension of motor axons. In addition, the optical transparency of the hydrogel allows simultaneous imaging of live cell functions, and as such, this material system should prove useful for studying fundamental aspects of neuronal development.

Graphical abstract: Synthetic hydrogel platform for three-dimensional culture of embryonic stem cell-derived motor neurons

Supplementary files

Article information

Article type
Paper
Submitted
05 Nov 2012
Accepted
09 Jan 2013
First published
24 Jan 2013

Biomater. Sci., 2013,1, 460-469

Synthetic hydrogel platform for three-dimensional culture of embryonic stem cell-derived motor neurons

D. D. McKinnon, A. M. Kloxin and K. S. Anseth, Biomater. Sci., 2013, 1, 460 DOI: 10.1039/C3BM00166K

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