Min Young Lee

Lee HY, et al. J Korean Med Sci. 2027 Feb;42:e17. https://doi.org/10.3346/jkms.2027.42.e17

Spiral ganglion neurons (SGNs) constitute the principal neural substrate for cochlear implantmediated auditory stimulation, and progressive SGN degeneration may limit the functional benefit of cochlear implantation. Stem-cell transplantation has therefore emerged as a potential strategy to preserve, replace, or increase the neuronal population within the spiral ganglion. Early studies demonstrated the survival and trophic effects of neural stem cells, followed by evidence of migration toward Rosenthal’s canal and modulation of SGN populations. Human mesenchymal stem cells and human embryonic stem-cell-derived otic progenitors subsequently provided the evidence of increased neuronal populations and functional auditory improvement. More recently, it has been shown that human dermal fibroblast-derived induced neural stem cells enhance cochlear neural structures, central auditory connectivity, and electrically evoke auditory responses. Collectively, these studies suggest that stem-cell therapy may improve the neural substrate for cochlear implantation not only through neuronal replacement but also through trophic preservation, targeted migration, and functional neural integration.

Photobiomodulation (PBM) is a non-thermal therapeutic modality in which low-intensity red or near-infrared light is used to modulate biological activity. Experimental inner-ear studies report preservation of auditory neurons, attenuation of vestibular injury, improved survival of transplanted stem cells, and changes in otic organoid differentiation. These observations raise the possibility that PBM may influence differentiation-associated cellular states in addition to providing cytoprotection. The classical mechanistic model proposes that photons interact with mitochondrial chromophores, particularly cytochrome c oxidase, leading to changes in respiration, ATP, reactive oxygen species (ROS), nitric oxide, calcium, and downstream signaling; however, a universal primary photoreceptor has not been established. In a 2020 mouse embryonic-stem-cell-derived otic-organoid study, PBM was associated with more organoid-like structures, increased hair-cell-associated markers, increased ROS, and lower Hes5 expression. The RNA-sequencing comparison pooled five embryoid bodies into one sample per condition, limiting biological replication and statistical inference. Accordingly, the Hes5 result should be regarded as exploratory and does not demonstrate direct Notch inhibition. Studies in other regenerative tissues show that PBM can engage ROS-dependent PI3K/AKT/GSK3β/β-catenin signaling, providing a mechanistic precedent rather than proof for the inner ear. This review therefore presents a testable working model in which PBM may connect mitochondrial and redox responses to Wnt/β-catenin and Notch/HES5 pathways during otic differentiation, while emphasizing that mature hair-cell regeneration, new SGN generation, and hearing restoration have not yet been established.

Compound muscle action potential (CMAP) recording provides an objective electrophysiological assessment of facial nerve function after injury. In rodent models, vibrissal CMAPs serve as quantitative surrogates of facial nerve integrity; however, practical descriptions of CMAP recording setups using widely available systems remain limited. In this study, we detail a practical and reproducible method for recording vibrissal CMAPs following direct stimulation of the facial nerve trunk in rats, using a BIOPAC-based system. CMAPs were recorded before and after unilateral facial nerve crush injury, followed by transection and epineural repair. Direct nerve trunk stimulation reliably elicited stable CMAP waveforms and supramaximal stimulation produced consistent responses suitable for longitudinal assessment. Baseline CMAP amplitudes were comparable to previously reported values. After facial nerve injury, CMAPs on the injured side were absent at 1 week, reappeared at 2 weeks, and increased further by 4 weeks. Because absolute CMAP amplitudes varied across recording sessions despite intact contralateral nerves, functional recovery was evaluated using left/right amplitude ratios. Single-peak CMAP amplitude was used to minimize waveform variability and stimulus-related artifacts. This method provides a straightforward and accessible approach for the electrophysiological assessment of facial nerve injury and recovery in experimental rodent models.

Objectives: Vestibular compensation supports recovery after acute unilateral vestibulopathy (UVP). A subset of patients develops direction-changing positional nystagmus (DCPN), which may reflect atypical central adaptation. The objective was to preliminarily investigate clinical characteristics of UVP patients with persistent vestibular weakness presenting with DCPN.Methods: Seventeen patients with persistent unilateral weakness on video head impulse test (mean 41 days post-onset) were analyzed retrospectively. Three exhibited DCPN (DCNp group) and were compared with 14 without DCPN (CONTROLp group) using vestibular testing and magnetic resonance imaging white matter hyperintensity (WMH) grading.Results: The DCNp group showed reduced spontaneous and head-shaking nystagmus amplitudes (p<0.05) and selectively decreased gains in the contralesional anterior and ipsilesional posterior canals (p<0.05). Periventricular WMH burden was significantly higher in the DCNp group (mean 3.0 vs. 1.8; p=0.001), while deep WMH did not differ.Conclusions: DCPN in UVP is linked to canal-specific gain asymmetry and increased periventricular WMH, suggesting impaired central compensation possibly influenced by cerebrovascular microstructural changes.

Neural regeneration remains a critical goal in regenerative medicine, especially for treating central nervous system injuries such as stroke, spinal cord injury, and neurodegenerative diseases. Mesenchymal stem cells (MSCs) have shown therapeutic potential through their capacity for differentiation and paracrine signaling; however, their clinical application is limited by low survival and engraftment rates. In this study, we investigated whether the therapeutic efficacy of human MSC (hMSC) spheroids could be enhanced through photobiomodulation (PBM). hMSCs were aggregated into three-dimensional spheroids and divided into four experimental groups: (1) untreated control spheroids, (2) spheroids treated with 660 nm PBM, (3) spheroids treated with 850 nm PBM, and (4) spheroids co-cultured with primary rat cortical neurons subjected to oxidative stress using hydrogen peroxide (H₂O₂). The PBM groups were exposed to red (660 nm) or near-infrared (NIR; 850 nm) light for 10 min. Neuronal viability and axonal regeneration were assessed. Our results demonstrated that PBM-treated hMSC spheroids significantly increased neuronal survival and axonal outgrowth compared to H₂O₂-only controls, particularly under high oxidative stress conditions. Notably, spheroids treated with 850 nm PBM exhibited the most robust neuroprotective effects. These findings suggest that PBM enhances mitochondrial activity and the secretion of neurotrophic factors by hMSC spheroids, thereby promoting neuroregeneration. This combinatorial strategy integrating PBM with 3D stem cell spheroid culture offers a promising avenue for developing advanced stem cell therapies for neurological disorders.

The development of auditory organoids represents a groundbreaking advancement in auditory research and regenerative medicine. These three-dimensional tissue structures, derived from pluripotent stem cells, replicate the architecture and function of the human inner ear, including the key sensory and neural cell types such as hair cells, supporting cells, and neurons. Auditory organoids enable researchers to study inner ear development, model genetic hearing disorders, and evaluate the effects of ototoxic drugs. Recent breakthroughs include the successful differentiation and functional validation of hair cell-like structures responsive to sound signals, as well as the integration of LGR5+ hair cell progenitor cells to enhance regenerative capacity. Despite significant progress, there remain many challenges of achieving full functional maturation, improving reproducibility, and scaling production for clinical applications. This emerging technology holds immense potential for understanding the inner ear biology, advancing personalized medicine, and developing novel therapies for hearing loss and balance disorders.

임상이비인후과(Journal of Clinical Otolaryngology Head and Neck Surgery)

Background: The regeneration of functional hair cells (HCs) remains a critical challenge in addressing sensorineural hearing loss. This study aimed to investigate the molecular and functional mechanisms driving stereocilia maturation within inner ear organoids (IEO) derived from homogenic Lgr5-positive progenitor cells (LPCs) and to compare outcomes with traditional heterotypic cultures.