Journal of Translational Neurosciences

Description

Neuroregeneration is made possible by transplanting Neural Stem Cells (NSCs) at the injury site of the Central Nerve System (CNS). The most challenging aspect of applying NSCs has been the low rates of proliferation, differentiation, and migration as well as long-term cell survival. The goal of a new multichannel Electrical Stimulation (ES) device is to improve the differentiation of Neural Stem Cells (NSCs) into mature neurons. Electrophysiological activity, neurite growth, BDNF concentration, and mature neuronal marker expression were all enhanced by ES at nanoscale topography in comparison to controls. The finding that ES enhanced autophagy signaling and promoted NSC-derived neuronal differentiation was confirmed by RNA sequencing. Arising confirmations showed that inadequate or exorbitant autophagy adds to neurite degeneration. Neuronal cells showed poor viability, reduced neurite outgrowth, and electrophysiological activity as a result of excessive ES current. Autophagy that is well-controlled not only prevents neurodegeneration but also regulates neurogenesis. By combining an appropriate ES condition with a balanced autophagy level in the cell culture system, the current NSC treatment protocol effectively enhanced NSC differentiation, maturation, and survival. After transplantation, such protreated NSC at the injured CNS site should have a significantly higher success rate.

Manipulation of NSC Physiological Reaction through ES

Neuron death, along with the resulting destruction of neural circuitry and loss of neuronal function, is caused by degenerative diseases and traumatic injuries to the Central Nerve System (CNS). Neural Stem Cells (NSCs), which are multipotent stem cells found in the Central Nervous System (CNS), can differentiate into a wide variety of more specialized CNS cells like neurons, astrocytes, and oligodendrocytes. Experiments have shown that neurons made from grafted NSCs can extend many axons from lesion sites to form synapses with host axons, which can act as neural relays across the lesion site to help improve function. In a variety of CNS diseases, such as ischemic stroke, traumatic brain injury, and neurodegenerative disease, exogenous NSCs transplantation had beneficial therapeutic effects. Although pretreatment of NSCs through exposure to small molecules and/or cytokines prior to transplantation has proven effective in promoting performance and enhancing functional recovery in pre-clinical in vivo settings, optimized and feasible protocols are still required to ensure the efficacy of NSC neurogenesis. However, current NSC-based approaches are blocked by a number of obstacles, including NSC migration involving, for example, proliferation, maturation, and integration. A new report found that electrical muscle feeling following nerve injury expanded the quantity of autophagosomes and the declaration of LC3-â?±autophagy markers while diminishing the degree of autophagy substrate protein P62 in distal nerve fragments. These researches attempted to connect electrical phenomena to autophagy, a well-known defense mechanism that recycles intracellular components to maintain cellular homeostasis. There is growing evidence that autophagy can reuse intracellular components to provide sufficient energy and metabolic substrates for NSC differentiation and that autophagy signaling is involved in the machinery that is related to the biological behaviors of NSCs. Although autophagy is thought to play a crucial role in the manipulation of NSC physiological reaction through ES, there has been limited research to verify the connection. ES involves the delivery of a low-level electrical current and/or electrical field to cells to produce an exogenous stimulus pressure.

Effectiveness of NSC Neurogenesis Prior to Transplantation

In this study, NSCs were cultured on an electrically conductive substrate made by layer-by-layer assembly of positively charged polymers and negatively charged Carbon Nanotubes (CNTs). A multi-chambered ES device was made to provide stable ES with parameters that could be changed in order to establish and investigate the connection between ES and enhanced autophagy. This study demonstrated that ES plays a crucial role in the promotion of neuronal differentiation and NSC maturation, a previously unknown function of autophagy. Our groundbreaking research sheds new light on the molecular mechanisms by which exogenous electric cues mediated by nanoscaled biomaterials could potentially boost NSC neurogenesis. It also sheds light on how ES could be used in the future to pre-condition NSCs before transplanting them for neural regeneration. By restoring connectivity through the induction of new relay circuits in lesions, NSCs have been demonstrated to hold significant promising and unique therapeutic plasticity in the treatment of severe CNS diseases and injuries. To increase the effectiveness of NSC neurogenesis prior to transplantation, NSCs have undergone treatment or training.