Controlling properties of human neural progenitor cells using 2D and 3D conductive polymer scaffolds

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.

Modulating the Electrical and Mechanical Microenvironment to Guide Neuronal Stem Cell Differentiation

“…Previous studies demonstrated that a single 1 h period of electrical stimulation results in sustained alteration of progenitor cell gene expression. [ 22,38 ] Utilizing these parameters for duration of stimulation, the voltage for electrical stimulation of the iPSCs was optimized by assessing neuronal differentiation from iPSCs for CGS stiffness (elasticity ranging from 3 to 12 kPa) and voltage (applied voltages ranging ±100 mV to ±3 V) ( Figure A; Figure S3 and Table S1, Supporting Information). Exposure to ±800 mV at 100 Hz for 1 h on the soft CGS (≈3 kPa) significantly increased the generation of TUJ1 + neurons without adverse cytotoxicity after 7d culture on the CGSs (Figure S3A–D and Table S1, Supporting Information).…”

“…These results further support prior studies which indicate that electrical stimulation can alter gene expression in progenitor cells and are a key mechanism for downstream effects. [ 22,38,39 ]…”

Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke

“…Electrical stimulation of hydrogel-immobilized hNPCs alters hNPCs genes involved in metabolic pathways and cell proliferation upregulates neurotrophic factors correlated with nerve regeneration, synaptic remodeling, and cell survival. These findings indicate that electrical stimulation modifies hNPC properties and may be beneficial to provide a novel therapy for neurological disease [ 173 ].…”

3D Printing and Bioprinting Nerve Conduits for Neural Tissue Engineering

“…Electrical stimulation enhances cell proliferation, migration, differentiation, and signaling connections between nerve cells, thereby enhancing neural regeneration and supporting the differentiation of stem cells into nerve cells [119,120]. Polypyrrole (PPy) [121,122], polyaniline (PANI) [123], poly (3,4-ethylenedioxythiophene) (PEDOT) [124,125] are the most promising conductive polymers for tissue engineering [126]. Many researchers indicated that conductive materials show good biocompatibility when co-cultured with cells in vitro [127].…”