Biology subjects

Sgroi, S.

Publications and source records attributed to Sgroi, S..

3 recordsLinked to original sources

bioRxiv2026

LGR5 and SOX2 expressing progenitor cells in the adult and aged human and mouse inner ear have the potential to produce Myosin 7A positive cells in vitro

Hearing loss and deafness as a result of hair cell loss cannot be restored due to the incapacity of spontaneous regeneration of these cells. Compounds that manipulate key signaling pathways can potentially regenerate cochlear hair cells. In order to test different compounds that promote hair cell regeneration in vitro models can be used. Three-dimensional cultures have allowed the expansion and experimentation of human and mouse inner ear organoids. This is mainly performed in the embryonic or the early postnatal developmental stage. However, since the majority of patients with hearing loss are adult, it is crucial to understand the adult inner ear regenerative capacity. Here, we evaluated progenitor cell markers in the adult human and mouse inner ear and the generation, expansion and differentiation of cochlear organoids derived from the adult human and mouse inner ear. Cochlear and vestibular sensory epithelium from adult humans; and from adult and aged mice express the progenitor markers SOX2 and LGR5; and can generate organoids in vitro. By optimizing the culture conditions, organoids derived from the cochlea and vestibular organ from adult human and adult and aged mouse differentiated to Myosin 7A positive cells. This indicates that the adult inner ear has regenerative capacity. These findings are encouraging for future regenerative therapies to cure hair cell-related hearing loss and deafness.

neuroscience↗

bioRxiv2025

Introducing a translationally relevant mouse model of radiosurgery-induced unilateral hearing loss

BackgroundStereotactic radiosurgery (SRS) is widely used to treat vestibular schwannomas but may cause irreversible hearing loss due to cochlear toxicity. The underlying mechanisms are not fully understood, and no effective otoprotective therapies exist. We aimed to establish a mouse model that replicates the clinical pattern of radiation-induced hearing loss. MethodsC57BL/6J mice (n=31) received 8 Gy (n=3), 16 Gy (n=5), 24 Gy (n=8), or 32 Gy (n=15) using the Leksell Gamma Knife ICON system. Targeting was based on the built-in cone-beam CT, co-registered with MRI and CT-based mouse atlases, to guide unilateral cochlea targeting. A single isocenter was placed lateral to the right cochlea, with the 80% isodose line traversing its medial edge. Auditory brainstem response (ABR) was measured at baseline and at 1 and 4 weeks post-SRS. A 32 Gy subgroup (n=7) was evaluated at 16 weeks. Histological analysis of cochleae was performed at 4 weeks in all groups and at 16 weeks in the long-term 32 Gy group. ResultsSRS was well tolerated, and the contralateral cochlea received a very low radiation dose. No ABR shifts were observed at 8 or 16 Gy, with only minimal histological changes. At 32 Gy, ABR threshold shifts at 22.6 and 32 kHz were evident by week 1 and worsened by week 4. Similar but milder effects occurred at 24 Gy. In the 32 Gy long-term subgroup, hearing loss progressed across all frequencies, most severely at high frequencies, alongside a sustained wave I amplitude decline. At 32 Gy, outer hair cells were reduced by 14% and 44% at 32 and 45.2 kHz, respectively, at 4 weeks, and by 38% and 80% at 16 weeks. Ribbon synapses were mildly reduced at 4 weeks and more markedly at 16 weeks in corresponding high-frequency regions. Spiral ganglion neuron density was mildly reduced at the basal and middle turns. All reported changes were statistically significant when compared to the contralateral ear. ConclusionsThis new model reproduces key features of SRS-induced cochlear toxicity, including unilateral, dose-dependent, and progressive hearing loss. It thus provides a valuable platform for investigating mechanisms and testing otoprotective strategies.

neuroscience↗

bioRxiv2025

Synergic microRNAs suppress human glioblastoma progression by modulating clinically relevant targets

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by therapy-resistant glioma stem-like cells (GSCs) and extensive infiltration into surrounding brain tissue. MicroRNAs (miRNAs) are post-transcriptional regulators of oncogenic pathways, but their tumor-suppressive function is frequently lost in GBM. This study explores a multimodal therapeutic approach by restoring a combination of miRNAs to exploit their synergistic effects against GBM. Using patient-derived GBM cells cultured under stem cell-permissive conditions, we demonstrate that miRNA restoration reduces tumor growth, limits invasiveness, stemness and enhances sensitivity to temozolomide. In vivo studies in an orthotopic xenograft mouse model of GBM confirm the therapeutic efficacy and low toxicity of the nanoformulated miRNAs, following local injection. Multi-omics and computational analyses on different GBM subtypes reveal that these miRNAs synergistically suppress tumor-promoting extracellular matrix interactions, particularly through the collagen pathway, and downregulate genes associated with GBM progression. The identified miRNA targets correlate with glioma grade and poor patient prognosis, further underscoring their therapeutic potential. These findings highlight the promise of combinatorial miRNA therapy as a novel strategy for GBM treatment and suggest new molecular targets for theragnostic development.

cancer biology↗