%0 Journal Article
%T Differentiation of Spiral Ganglion Neurons from Human Dental Pulp Stem Cells: A Further Step towards Autologous Auditory Nerve Recovery.
%+ Laboratoire de Bioingénierie et NanoSciences (LBN)
%+ Laboratoire Charles Coulomb (L2C)
%+ Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
%+ CHU Montpellier = Montpellier University Hospital
%+ Université de Montpellier (UM)
%A Messat, Yassine
%A Martin Fernandez, Marta
%A Assou, Said
%A Chung, Keshi
%A Guérin, Frederic
%A Gergely, Csilla
%A Cuisinier, Frédéric
%A Zine, Azel
%< avec comité de lecture
%@ 1661-6596
%J International Journal of Molecular Sciences
%I MDPI
%V 25
%N 16
%P 9115
%8 2024-08-22
%D 2024
%R 10.3390/ijms25169115
%M 39201803
%K adult dental pulp stem cells
%K differentiation
%K human otic neural progenitors
%K spiral ganglion neurons
%K mechanical properties
%K cell therapy
%Z Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
%Z Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
%Z Life Sciences [q-bio]/Development BiologyJournal articles
%X 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 TGFβ 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.
%G English
%2 https://hal.science/hal-04676159v1/document
%2 https://hal.science/hal-04676159v1/file/main.pdf
%L hal-04676159
%U https://hal.science/hal-04676159
%~ INSERM
%~ CNRS
%~ L2C
%~ UNIV-MONTPELLIER
%~ LBN
%~ UM-2015-2021
%~ UM-EPE