{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:19:42Z","timestamp":1790025582785,"version":"4.0.1"},"reference-count":57,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cla Fondation des Gueules-Cass\u00e9es\u201d Paris, France","award":["GC 210846"],"award-info":[{"award-number":["GC 210846"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The degeneration of spiral ganglion neurons (SGNs), which convey auditory signals from hair cells to the brain, can be a primary cause of sensorineural hearing loss (SNHL) or can occur secondary to hair cell loss. Emerging therapies for SNHL include the replacement of damaged SGNs using stem cell-derived otic neuronal progenitors (ONPs). However, the availability of renewable, accessible, and patient-matched sources of human stem cells is a prerequisite for successful replacement of the auditory nerve. In this study, we derived ONP and SGN-like cells by a reliable and reproducible stepwise guidance differentiation procedure of self-renewing human dental pulp stem cells (hDPSCs). This in vitro differentiation protocol relies on the modulation of BMP and TGF\u03b2 pathways using a free-floating 3D neurosphere method, followed by differentiation on a Geltrex-coated surface using two culture paradigms to modulate the major factors and pathways involved in early otic neurogenesis. Gene and protein expression analyses revealed efficient induction of a comprehensive panel of known ONP and SGN-like cell markers during the time course of hDPSCs differentiation. Atomic force microscopy revealed that hDPSC-derived SGN-like cells exhibit similar nanomechanical properties as their in vivo SGN counterparts. Furthermore, spiral ganglion neurons from newborn rats come in close contact with hDPSC-derived ONPs 5 days after co-culturing. Our data demonstrate the capability of hDPSCs to generate SGN-like neurons with specific lineage marker expression, bipolar morphology, and the nanomechanical characteristics of SGNs, suggesting that the neurons could be used for next-generation cochlear implants and\/or inner ear cell-based strategies for SNHL.<\/jats:p>","DOI":"10.3390\/ijms25169115","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T05:16:24Z","timestamp":1724649384000},"page":"9115","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Differentiation of Spiral Ganglion Neurons from Human Dental Pulp Stem Cells: A Further Step towards Autologous Auditory Nerve Recovery"],"prefix":"10.3390","volume":"25","author":[{"given":"Yassine","family":"Messat","sequence":"first","affiliation":[{"name":"LBN, Laboratory of Bioengineering and Nanoscience, University of Montpellier, 34193 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Martin-Fernandez","sequence":"additional","affiliation":[{"name":"L2C, Laboratoire Charles Coulomb, University of Montpellier, CNRS, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-7995","authenticated-orcid":false,"given":"Said","family":"Assou","sequence":"additional","affiliation":[{"name":"IRMB, Institute for Regenerative Medicine & Biotherapy, University of Montpellier, INSERM, CHU Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keshi","family":"Chung","sequence":"additional","affiliation":[{"name":"LBN, Laboratory of Bioengineering and Nanoscience, University of Montpellier, 34193 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Gu\u00e9rin","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, University of Montpellier, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csilla","family":"Gergely","sequence":"additional","affiliation":[{"name":"L2C, Laboratoire Charles Coulomb, University of Montpellier, CNRS, 34095 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Cuisinier","sequence":"additional","affiliation":[{"name":"LBN, Laboratory of Bioengineering and Nanoscience, University of Montpellier, 34193 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9691-5173","authenticated-orcid":false,"given":"Azel","family":"Zine","sequence":"additional","affiliation":[{"name":"LBN, Laboratory of Bioengineering and Nanoscience, University of Montpellier, 34193 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s10162-020-00761-4","article-title":"Relationships between Intrascalar Tissue, Neuron Survival, and Cochlear Implant Function","volume":"21","author":"Swiderski","year":"2020","journal-title":"J. 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