Dataset Information

Graphene-polymer nanofibers enable optically induced electrical maturation in stem cell-derived cardiomyocytes and brain organoids

ABSTRACT: Pluripotent stem cell (PSC)-derived electrically excitable cells provide a unique window into human disease and development, but they remain electrically immature compared to their in vivo counterparts, partially due to the lack of chronic stimulation. New classes of on-demand, electrically active biomaterials are being employed to enhance cell functions, and here, we fabricated biocompatible, electrospun polymer nanofibers containing light-reactive reduced graphene oxide (rGO). Fiber size, stiffness, and electrical conductivity scaled with rGO concentration which in turn produced conduction-dependent effects in PSC-derived cardiomyocytes and neurons; with acute light stimulation on scaffolds containing rGO, cardiomyocytes exhibited more calcium handling activity and were more synchronous, and neurons showed more peaks with higher frequency. Chronic repetitive, daily light stimulation of nanofibers integrated into mature brain organoids caused organoids to become increasingly more electrically responsive to stimulation over time, mature synapses of excitable neurons, and activate photoreceptor lineage pathways. This work outlines a tunable method where the electrical function of electrically excitable, PSC-derived cells can be titrated with rGO fibers and light stimulation, and it suggests that repetitive light stimulation may provide a novel method for retinal cell differentiation in organoids.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268981 | GEO | 2024/06/08

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Despite efforts to mature human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) for disease modeling and high throughput screening, cells remain immature and may not reflect adult biology. Recent advancements utilize electro-mechanical and paracrine stimulation to functionally mature cardiomyocytes, but the resulting engineered constructs continue to lack a microenvironment conducive to electrical signal propagation and maturity. Conductive polymers are attractive candidates to facilitate electrical communication between gaps in sparse hPSC-CM clusters or between hPSC-CMs to repair conduction defects. To create a conductive polymer platform for improved electrical signal propagation between hPSC-CMs and achieve electrical maturity, we electrospun poly(3,4-ethylendioxythiophene):polystyrene sulfonate (PEDOT:PSS) blended with 8% (w/v) poly(vinyl alcohol) (PVA). Matrix fiber structure remained stable over 4 weeks in buffer, stiffness remains near cardiac stiffness in vivo, and electrical conductivity scaled with PEDOT:PSS concentration. When fibroblasts were added to fibers, cells had higher initial attachment to PEDOT:PSS compared to PVA-only scaffolds, and after 5 days, over 90% of fibroblasts remained viable on PEDOT:PSS scaffolds compared to PVA-only scaffolds. Electrically excitable hPSC-CMs cultured on conductive substrates exhibited an upregulation of cardiac and muscle-related genes as opposed to non-conductive substrates. These cells further displayed increased desmoplakin (DP) localization on conductive scaffolds, indicating an improvement in the mechanical stability of our hPSC-CMs. Sarcomere organization also scaled with increasing PEDOT:PSS concentration, even in sub-monolayer cell densities, suggesting that improved organization of the contractile machinery in these cells was due to the electrical condition of the matrix. Calcium handling indicated higher calcium flux with a shorter time to peak, further suggesting improved electrical maturity, even when sub-confluent. Taken together, these data suggest that PEDOT:PSS/PVA scaffolds are stable, of a stiffness relevant to cardiomyocytes, and supportive of electrical coupling even in the absence of a monolayer, which may improve cardiac disease modeling and drug development.

Dataset Information

Graphene-polymer nanofibers enable optically induced electrical maturation in stem cell-derived cardiomyocytes and brain organoids

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure