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

Abstract

The application of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine can be limited by the prolonged times required for functional human neuronal differentiation and traditional 2D culture techniques. Here, a conductive graphene scaffold (CGS) to modulate mechanical and electrical signals to promote human iPSC‐derived neurons is presented. The soft CGS with cortex‐like stiffness (≈3 kPa) and electrical stimulation (±800 mV/100 Hz for 1 h) incurs a fivefold improvement in the rate (14d) of generating iPSC‐derived neurons over some traditional protocols, with an increase in mature cellular markers and electrophysiological characteristics. Consistent with other culture conditions, it is found that the pro‐neurogenic effects of mechanical and electrical stimuli rely on RhoA/ROCK signaling and de novo ciliary neurotrophic factor (CNTF) production respectively. Thus, the CGS system creates a combined physical and continuously modifiable, electrical niche to efficiently and quickly generate iPSC‐derived neurons.

Insights into the conformation changes of SARS-CoV-2 spike receptor-binding domain on graphene

“…Some people proposed to add graphene nanofilms into the masks to more effectively block the spread of the virus. Byeongtaek Oh et al studied the application of graphene in promoting neuronal stem cell differentiation [33] . Graphene can be made into magnetic nanocapsules, which is able to deliver oral drugs to the stomach site-selective [34] .…”

Design Artificial Stem Cell Nests for Stem Cell Niche in a Microfluidic Petri Dish Programmed by a Cell Phone

“…[ 36 ] The niche brings intractable complexity. We must also consider the electrical niche [ 37 ] for generating stem cell‐derived neurons, macrophages [ 38 ] for the muscle stem cell niche and the pathogen's interaction with the stem cell niche for potential inflammation. [ 39 ] Biologists even consider the niche ecology of cancer differentiation therapy.…”

Extrapolating neurogenesis of mesenchymal stem/stromal cells on electroactive and electroconductive scaffolds to dental and oral-derived stem cells

“…Otherwise, it is expected that all electrical stimuli would be transduced into biological signals by voltage-gated ion channels 34 , 35 or cell surface receptors (i.e. Notch1 36 and CNTF receptor 37 ) via a number of pro-neurogenic signaling pathways (Fig. 1 ).…”

“…1 ). These include the cAMP-PKA signaling cascade, 34 , 38 the PI3k-Akt signaling cascade, 39 the Notch signaling cascade, 36 and autocrine CNTF signaling, 37 which have been described in detail in our review article. 33 Based on the scientific literature, 39 – 41 it would appear that both transmembrane and soluble isoforms of adenylyl cyclase play key roles in neuronal function and neurogenic differentiation via the cAMP-PKA signaling axis.…”