Nanoscale Optoregulation of Neural Stem Cell Differentiation by Intracellular Alteration of Redox Balance

Abstract

Regulation of stem cell (SC) fate, a decision between self-renewal and differentiation, is of immense importance in regenerative medicine and has been proven to be a powerful stimulus regulating many cell functions influencing the SC fate. This study uses triphenylphosphonium-functionalized gold nanoparticles (TPP-AuNPs) to explore the interplay of intracellular electromagnetic (EM) exposure and the SC fate. Localized EM waves are generated inside neural stem cells (NSCs) to stimulate TPP-AuNPs (AuNPs), targeting the mitochondria through inducing reactive oxygen species and differentiating these cells into neurons. Following laser irradiation of TPP-AuNPs-transfected NSCs, their differentiation to neurons is monitored by tracing the relevant markers both at the genetic and protein levels. The electrophysiology technique is further used to examine the functionality of neurons. The results confirm that TPP-AuNPs subjected to electromotive forces have the potential to regulate cellular fate, although further investigations are still required to shed light on the mechanisms underlying the interaction of EM-stimulated TPP-AuNPs on cellular fate to design highly adjustable cell differentiation and reprogramming methods.

Electrophysiology Read-Out Tools for Brain-on-Chip Biotechnology

“…This technique is proving a powerful tool in the era of stem cell biotechnology and brain tissue bioengineering [ 390 ]. Classic optogenetics has also proved useful to regulate gene expression [ 391 ], guide stem cell fate during development [ 392 , 393 ], study and modulate signaling pathways involved in embryogenesis [ 394 , 395 ]. Chemical optogenetics has been used to modulate immune responses [ 396 ] and intracellular signaling pathways, such as cAMP synthesis [ 397 ], GTPase-mediated cytoskeletal function enabling photocontrol of cell motility and shape [ 398 ], and the versatile tunable light-controlled protein tags enabling regulation of a variety of signaling pathways [ 399 ].…”

Bioprocessing of Mesenchymal Stem Cells and Their Derivatives: Toward Cell-Free Therapeutics

“…For example, exposure of Wharton jelly-derived MSCs to EMF (1.8 mT, 75 Hz, 8 h/day for 21 days) increased cell division and cell densities, induced early chondrogenic differentiation, and increased collagen II expression levels [ 107 ]. Similarly, though dependent on intensity, time of exposure, and frequency of EMF, EMF exposure has been used to enhance osteogenic and neural differentiation [ 108 – 110 ], impact cell metabolism and structure [ 111 ], and increase cell viability [ 112 ].…”

Emerging Strategies for Stem Cell Lineage Commitment in Tissue Engineering and Regenerative Medicine

“…Studies on neural differentiation of human bone marrow MSCs in response to continuous, sinusoidal, extremely low-frequency electromagnetic fields (ELF-EMF; 5 mT) showed a reactive oxygen species (ROS)-dependent growth factor signaling mechanism . In addition to external EMF, localized generation of EMFs around mitochondria using gold nanoparticles can regulate the fate of NSCs . Chondrogenic and osteogenic differentiation of MSCs induced by electromagnetic fields have also been successful.…”

“…129 In addition to external EMF, localized generation of EMFs around mitochondria using gold nanoparticles can regulate the fate of NSCs. 130 Chondrogenic 131 and osteogenic 132 differentiation of MSCs induced by electromagnetic fields have also been successful. The exposure modality of stem cells to ELF-EMF may be either continuous or pulsed and has been reported to have different differentiation outcomes.…”