Abstract
Human induced pluripotent stem cell-derived neural progenitor cells (hNPCs) are a promising cell source for stem cell transplantation to treat neurological diseases such as stroke and peripheral nerve injuries. However, there have been limited studies investigating how the dimensionality of the physical and electrical microenvironment affects hNPC function. In this study, we report the fabrication of two- and three-dimensional (2D and 3D respectively) constructs composed of a conductive polymer to compare the effect of electrical stimulation of hydrogel-immobilized hNPCs. The physical dimension (2D vs 3D) of stimulating platforms alone changed the hNPCs gene expression related to cell proliferation and metabolic pathways. The addition of electrical stimulation was critical in upregulating gene expression of neurotrophic factors that are important in regulating cell survival, synaptic remodeling, and nerve regeneration. This study demonstrates that the applied electrical field controls hNPC properties depending on the physical nature of stimulating platforms and cellular metabolic states. The ability to control hNPC functions can be beneficial in understanding mechanistic changes related to electrical modulation and devising novel treatment methods for neurological diseases.
Highlights
The native stem cell niche presents a complex physiochemical microenvironment involving physical, chemical, and electrical signals that can dictate stem cell fate and behaviors
We showed that 2D and 3D electrically-stimulated hNPCs exhibited significant changes in the expression of neurotrophic factors under a brief electrical stimulation
Our immunofluorescent data showed a uniform expression of these markers, indicating the successful differentiation of human induced pluripotent stem cells (hiPSCs) into hNPCs
Summary
The native stem cell niche presents a complex physiochemical microenvironment involving physical (i.e. mechanical stress), chemical (i.e. growth factors), and electrical signals that can dictate stem cell fate and behaviors. The LDH assay showed that the percentage of dead cells was 1.6 ± 0.5% and 3.1 ± 1.2% for hNPCs on 2D PPy films, and 19 ± 4.2% and 16 ± 2.8% for 3D PPy tubes under unstimulated and stimulated conditions, respectively (Fig. 3a).
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