Peripheral nerve injury is a major challenge in clinical treatment due to the limited intrinsic capacity for nerve regeneration. Tissue engineering approaches offer promising solutions by providing biomimetic scaffolds and cell sources to promote nerve regeneration. In the present work, we investigated the potential role of skin-derived progenitors (SKPs), which are induced into neurons and Schwann cells (SCs), and their extracellular matrix in tissue-engineered nerve grafts (TENGs) to enhance peripheral neuroregeneration. SKPs were induced to differentiate into neurons and SCs in vitro and incorporated into nerve grafts composed of a biocompatible scaffold including chitosan neural conduit and silk fibroin filaments. In vivo experiments using a rat model of peripheral nerve injury showed that TENGs significantly enhanced nerve regeneration compared to the scaffold control group, catching up with the autograft group. Histological analysis showed improved axonal regrowth, myelination and functional recovery in animals treated with these TENGs. In addition, immunohistochemical staining confirmed the presence of induced neurons and SCs within the regenerated nerve tissue. Our results suggest that SKP-induced neurons and SCs in tissue-engineered nerve grafts have great potential for promoting peripheral nerve regeneration and represent a promising approach for clinical translation in the treatment of peripheral nerve injury. Further optimization and characterization of these engineered constructs is warranted to improve their clinical applicability and efficacy.

Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions. Preclinical studies have demonstrated ADSC transplantation\'s effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements. Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.

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Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and INa+/IK+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

Spinal cord injury (SCI) is a debilitating condition that is associated with long-term physical and functional disability. Our understanding of the pathogenesis of SCI has evolved significantly over the past three decades. In parallel, significant advances have been made in optimizing the management of patients with SCI. Early surgical decompression, adequate bony decompression and expansile duraplasty are surgical strategies that may improve neurological and functional outcomes in patients with SCI. Furthermore, advances in the non-surgical management of SCI have been made, including optimization of hemodynamic management in the critical care setting. Several promising therapies have also been investigated in pre-clinical studies, with some being translated into clinical trials. Given the recent interest in advancing precision medicine, several investigations have been performed to delineate the role of imaging, cerebral spinal fluid (CSF) and serum biomarkers in predicting outcomes and curating individualized treatment plans for SCI patients. Finally, technological advancements in biomechanics and bioengineering have also found a role in SCI management in the form of neuromodulation and brain-computer interfaces.

Despite the intrinsic repair of peripheral nerve injury (PNI), it is important to carefully monitor the process of peripheral nerve repair, as peripheral nerve regeneration is slow and incomplete in large traumatic lesions. Hence, mesenchymal stem cells (MSCs) with protective and regenerative functions are utilized in synergy with innovative micro/nano technologies to enhance the regeneration process of peripheral nerves. Nonetheless, as MSCs are assessed using standard regenerative criteria including sensory-motor indices, structural features, and morphology, it is challenging to differentiate between the protective and regenerative impacts of MSCs on neural tissue. This study aims to analyze the process of nerve regeneration, particularly the performance of MSCs with and without synergistic approaches. It also focuses on the paracrine secretions of MSCs and their conversion into neurons with functional properties that influence nerve regeneration after PNI. Furthermore, the study explores new ideas for nerve regeneration after PNI by considering the synergistic effect of MSCs and therapeutic compounds, neuronal cell derivatives, biological or polymeric conduits, organic/inorganic nanoparticles, and electrical stimulation. Finally, the study highlights the main obstacles to developing synergy in nerve regeneration after PNI and aims to open new windows based on recent advances in neural tissue regeneration.

Here, we establish that plasticity exists within the postnatal enteric nervous system by demonstrating the reinnervation potential of post-mitotic enteric neurons (ENs). Employing BAF53b-Cre mice for selective neuronal tracing, the reinnervation capabilities of mature postnatal ENs are shown across multiple model systems. Isolated ENs regenerate neurites in vitro, with neurite complexity and direction influenced by contact with enteric glial cells (EGCs). Nerve fibers from transplanted ENs exclusively interface and travel along EGCs within the muscularis propria. Resident EGCs persist after Cre-dependent ablation of ENs and govern the architecture of the myenteric plexus for reinnervating ENs, as shown by nerve fiber projection tracing. Transplantation and optogenetic experiments in vivo highlight the rapid reinnervation potential of post-mitotic neurons, leading to restored gut muscle contractile activity within 2 weeks. These studies illustrate the structural and functional reinnervation capacity of post-mitotic ENs and the critical role of EGCs in guiding and patterning their trajectories.

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UNASSIGNED: Pre-clinical animal experiment.
UNASSIGNED: In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI.
UNASSIGNED: The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe2+ levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso-Beattie-Bresnahan test.
UNASSIGNED: Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group (p < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups (p < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group (p < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups (p < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI (p < 0.05).
UNASSIGNED: Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.

Artificial intelligence (AI) and machine learning (ML) show promise in various medical domains, including medical imaging, precise diagnoses, and pharmaceutical research. In neuroscience and neurosurgery, AI/ML advancements enhance brain-computer interfaces, neuroprosthetics, and surgical planning. They are poised to revolutionize neuroregeneration by unraveling the nervous system\'s complexities. However, research on AI/ML in neuroregeneration is fragmented, necessitating a comprehensive review. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, 19 English-language papers focusing on AI/ML in neuroregeneration were selected from a total of 247. Two researchers independently conducted data extraction and quality assessment using the Mixed Methods Appraisal Tool (MMAT) 2018. Eight studies were deemed high quality, 10 moderate, and four low. Primary goals included diagnosing neurological disorders (35%), robotic rehabilitation (18%), and drug discovery (12% each). Methods ranged from analyzing imaging data (24%) to animal models (24%) and electronic health records (12%). Deep learning accounted for 41% of AI/ML techniques, while standard ML algorithms constituted 29%. The review underscores the growing interest in AI/ML for neuroregenerative medicine, with increasing publications. These technologies aid in diagnosing diseases and facilitating functional recovery through robotics and targeted stimulation. AI-driven drug discovery holds promise for identifying neuroregenerative therapies. Nonetheless, addressing existing limitations remains crucial in this rapidly evolving field.