Abstract
Nerve injuries and neurodegenerative disorders remain serious challenges, owing to the poor treatment outcomes of in situ neural stem cell regeneration. The most promising treatment for such injuries and disorders is stem cell-based therapies, but there remain obstacles in controlling the differentiation of stem cells into fully functional neuronal cells. Various biochemical and physical approaches have been explored to improve stem cell-based neural tissue engineering, among which electrical stimulation has been validated as a promising one both in vitro and in vivo. Here, we summarize the most basic waveforms of electrical stimulation and the conductive materials used for the fabrication of electroactive substrates or scaffolds in neural tissue engineering. Various intensities and patterns of electrical current result in different biological effects, such as enhancing the proliferation, migration, and differentiation of stem cells into neural cells. Moreover, conductive materials can be used in delivering electrical stimulation to manipulate the migration and differentiation of stem cells and the outgrowth of neurites on two- and three-dimensional scaffolds. Finally, we also discuss the possible mechanisms in enhancing stem cell neural differentiation using electrical stimulation. We believe that stem cell-based therapies using biocompatible conductive scaffolds under electrical stimulation and biochemical induction are promising for neural regeneration.
Highlights
Nerve diseases, including axon loss, nerve injury, and degenerative nerve disease, are a severe economic burden to society
Several studies have demonstrated that the PI3K/Akt and mitogenactivated protein kinase (MAPK)/extracellular signalregulated kinase (ERK) pathways are involved in regulating neural stem cells (NSCs) migration under electrical stimulation (ES) [42, 102,103,104]
Rajnicek et al found that neuronal growth cones migrating toward the cathode were regulated by cell division cycle 42 (Cdc42), Rac, and Rho and not by the PI3K and MAPK/ERK signaling pathways, which were found in the electric field guidance of nonneuronal cells [105]
Summary
Nerve diseases, including axon loss, nerve injury, and degenerative nerve disease, are a severe economic burden to society. Current medical and surgical strategies and physiotherapy are common treatments for nerve diseases. These strategies alleviate pain after nerve injury, maintain the continuity of nerves, and delay disease progression but are difficult to perform, time-consuming, expensive, and do not always result in sufficient functional recovery and nerve regeneration. Numerous clinical trials have been initiated to evaluate the safety and efficacy of stem cell therapy in patients with various nerve diseases. A prerequisite in applying stem cells to nerve tissue engineering is controlling the differentiation of stem cells into neural cells with precision and efficacy. Low-frequency ES has been proven effective clinically in regenerating nerves, leading to regeneration and functional recovery [5]; the effects of ES on stem cell neural differentiation in. We discuss here our perspectives on the future of the clinical application of ES on stem cells for the treatment of nerve diseases
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