Human Rett-derived neuronal progenitor cells in 3D graphene scaffold as an in vitro platform to study the effect of electrical stimulation on neuronal differentiation

Abstract

Studies of electrical stimulation therapies for the treatment of neurological disorders, such as deep brain stimulation, have almost exclusively been performed using animal-models. However, because animal-models can only approximate human brain disorders, these studies should be supplemented with an in vitro human cell-culture based model to substantiate the results of animal-based studies and further investigate therapeutic benefit in humans. This study presents a novel approach to analyze the effect of electrical stimulation on the neurogenesis of patient-induced pluripotent stem cell (iPSC) derived neural progenitor cell (NPC) lines, in vitro using a 3D graphene scaffold system. The iPSC-derived hNPCs used to demonstrate the system were collected from patients with Rett syndrome, a debilitating neurodevelopmental disorder. The graphene scaffold readily supported both the wild-type and Rett NPCs. Electrical stimulation parameters were optimized to accommodate both wild-type and Rett cells. Increased cell maturation and improvements in cell morphology of the Rett cells was observed after electrical stimulation. The results of the pilot study of electrical stimulation to enhance Rett NPCs neurogenesis were promising and support further investigation of the therapy. Overall, this system provides a valuable tool to study electrical stimulation as a potential therapy for neurological disorders using patient-specific cells.

Electroactive Scaffolds for Neurogenesis and Myogenesis: Graphene‐Based Nanomaterials

“…3D graphene foams (GFs) with high porosity, proper mechanical properties, unique topography, and excellent conductivity were demonstrated to be multifunctional scaffolds to support the growth and differentiation of neural cells, and study neuronal connectivity, functionalities, etc . 3D GFs synthesized by CVD method with laminin precoating were highly biocompatible and improved NSCs adhesion and proliferation compared to 2D graphene films, probably due to their irregular surface topography and 3D porous structure that are beneficial for cell–substrate adhesion ( Figure A) .…”

Graphene-Based Nanomaterials: From Production to Integration With Modern Tools in Neuroscience

“…Indeed, those nanomaterials significantly affect neurite branching and synapses during stem cell differentiation to neurons (Defteralí et al, 2016a,b). Similarly, changes during the differentiation of human induced pluripotent stem cells into multiple somatic cell lineages have been shown in graphene-treated samples (Yoo et al, 2014; Hu et al, 2015; Choi et al, 2016; Lee et al, 2016; Rodriguez-Losada et al, 2017; Wang et al, 2017; Nguyen et al, 2018; Sánchez-González et al, 2018; Saburi et al, 2019). The specific effects of Gr/GO seem to be variable even within stem cell type, but overall results collectively suggest that Gr holds promise as a scaffold material for regenerative medicine and stem cell-based technologies.…”

Biomedical Applications of Graphene-Based Structures

“…Another approach in tissue engineering is to use pure 3D G foams that are produced via metal-free methods [ 111 ]. Pure G foam was examined as an electrically conductive scaffold for testing the effects of the electrical stimulation of human neural progenitor cells (hNPCs) that were derived from a patient’s fibroblasts that were available in the cell bank.…”

“…Cells after electrical stimulation were found to have larger average soma than cells without any electrical stimulation. Electrical stimulation of hNPCs cultured on a 3D G scaffold caused an increase in their differentiation and maturation into neurons [ 111 ]. GFs are also efficiently used to form regeneration tubes for neural tissue engineering [ 112 ].…”