{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:49:44Z","timestamp":1768506584206,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,24]]},"group-title":"Neuroscience","reference-count":43,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Animal studies have shown that the supporting-cells surviving in the organ of Corti after cochlear insult can be transdifferentiated into hair cells as a treatment for sensorineural hearing loss. Clinical trials of small-molecule therapeutics have been undertaken, but little is known about how to predict the pattern and degree of supporting-cell survival based on audiogram, hearing loss etiology or any other metric obtainable pre-mortem. To address this, we systematically assessed supporting-cell and hair cell survival, as a function of cochlear location in 274 temporal bone cases from the archives at the Massachusetts Eye and Ear and compared the histopathology with the audiograms and hearing-loss etiologies. Results showed that supporting-cell survival was always significantly greater in the apical half than the basal half of the cochlea, that inner pillars were more robust than outer pillars or Deiters\u2019 cells, and that total replacement of all supporting cells with a flat epithelium was rare outside of the extreme basal 20% of the cochlea. Supporting cell survival in the basal half of the cochlea was better correlated with the slope of the audiogram than with the mean high-frequency threshold per se: i.e. survival was better with flatter audiograms than with steeply down-sloping audiograms. Cochlear regions with extensive hair cell loss and exceptional supporting cell survival were most common in cases with hearing loss due to ototoxic drugs. Such cases also tended to have less pathology in other functionally critical structures, i.e. spiral ganglion neurons and the stria vascularis.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>Supporting cell survival was systematically assessed in 274 human cochleas<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Supporting cell survival was better with flat than with down-sloping audiograms<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Supporting cell survival was most robust when hearing loss was from ototoxic drugs<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Ototoxic cases also showed less pathology in other critical cochlear structures<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>The data can inform clinical trials for regeneration via supporting cell conversion<\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2023.04.24.538119","type":"posted-content","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T20:50:16Z","timestamp":1682369416000},"source":"Crossref","is-referenced-by-count":0,"title":["Supporting-cell vs. hair-cell survival in the human cochlea: Implications for regenerative therapies"],"prefix":"10.64898","author":[{"given":"Charanjeet","family":"Kaur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"McKayla","family":"Van Orden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer T.","family":"O\u2019Malley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-zhe","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Charles","family":"Liberman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"3","key":"2023042709452564000_2023.04.24.538119v1.1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.stemcr.2014.01.008","article-title":"Lgr5-positive supporting cells generate new hair cells in the postnatal cochlea","volume":"2","year":"2014","journal-title":"Stem Cell Reports"},{"key":"2023042709452564000_2023.04.24.538119v1.2","first-page":"231","article-title":"Cellular pattern and nerve supply of the human organ of Corti","volume":"Suppl 236","year":"1968","journal-title":"Acta Otolaryngol"},{"key":"2023042709452564000_2023.04.24.538119v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-011-0267-2"},{"key":"2023042709452564000_2023.04.24.538119v1.4","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1978.41.2.365"},{"issue":"1","key":"2023042709452564000_2023.04.24.538119v1.5","doi-asserted-by":"crossref","first-page":"E36","DOI":"10.1002\/lary.27539","article-title":"Supporting cell survival after cochlear implant surgery","volume":"129","year":"2019","journal-title":"Laryngoscope"},{"key":"2023042709452564000_2023.04.24.538119v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-013-0396-x"},{"key":"2023042709452564000_2023.04.24.538119v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(85)90121-2"},{"key":"2023042709452564000_2023.04.24.538119v1.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3944-15.2016"},{"issue":"6 PT. 1","key":"2023042709452564000_2023.04.24.538119v1.9","first-page":"725","article-title":"Degeneration patterns in human ears exposed to noise","volume":"85","year":"1976","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"2023042709452564000_2023.04.24.538119v1.10","first-page":"1","article-title":"Aminoglycoside-induced cochlear pathology in man","volume":"383","year":"1981","journal-title":"Acta Otolaryngol Suppl"},{"issue":"3","key":"2023042709452564000_2023.04.24.538119v1.11","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/MAO.0000000000001686","article-title":"Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes Following Cochlear Implantation in the Human: An Immunohistochemical Study","volume":"39","year":"2018","journal-title":"Otol Neurotol"},{"key":"2023042709452564000_2023.04.24.538119v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(88)90018-4"},{"key":"2023042709452564000_2023.04.24.538119v1.13","doi-asserted-by":"publisher","DOI":"10.1121\/1.381736"},{"key":"2023042709452564000_2023.04.24.538119v1.14","first-page":"1","article-title":"Acoustic trauma in cats. Cochlear pathology and auditory-nerve activity","volume":"358","year":"1978","journal-title":"Acta Otolaryngol Suppl"},{"key":"2023042709452564000_2023.04.24.538119v1.15","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0b013e31819a8827"},{"key":"2023042709452564000_2023.04.24.538119v1.16","doi-asserted-by":"crossref","unstructured":"Lobarinas, E. , R. Salvi and D. Ding (2013). \u201cInsensitivity of the audiogram to carboplatin induced inner hair cell loss in chinchillas.\u201d Hearing research.","DOI":"10.1016\/j.heares.2013.03.012"},{"key":"2023042709452564000_2023.04.24.538119v1.17","first-page":"1293","article-title":"Human cochlear changes in noise induced hearing loss","volume":"9","year":"1976","journal-title":"Laryngoscope LXXXVI"},{"issue":"7","key":"2023042709452564000_2023.04.24.538119v1.18","doi-asserted-by":"crossref","first-page":"e849","DOI":"10.1097\/MAO.0000000000003120","article-title":"Improved Speech Intelligibility in Subjects With Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study","volume":"42","year":"2021","journal-title":"Otol Neurotol"},{"key":"2023042709452564000_2023.04.24.538119v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.01.066"},{"key":"2023042709452564000_2023.04.24.538119v1.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408064111"},{"key":"2023042709452564000_2023.04.24.538119v1.21","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-008-0111-5"},{"key":"2023042709452564000_2023.04.24.538119v1.22","unstructured":"Merchant, S. N. and J. B. Nadol (2010). Schuknecht\u2019s Pathology of the Ear, 3rd Edition. Shelton, CT, People\u2019s Medical Publishing House - USA."},{"key":"2023042709452564000_2023.04.24.538119v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.032"},{"key":"2023042709452564000_2023.04.24.538119v1.24","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-009-0183-x"},{"key":"2023042709452564000_2023.04.24.538119v1.25","doi-asserted-by":"publisher","DOI":"10.1288\/00005537-198807000-00014"},{"key":"2023042709452564000_2023.04.24.538119v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(91)90034-7"},{"key":"2023042709452564000_2023.04.24.538119v1.27","first-page":"14","article-title":"Ganglion cell and \u2018dendrite\u2019 populations in electric acoustic stimulation ears","volume":"67","year":"2010","journal-title":"Adv Otorhinolaryngol"},{"issue":"6","key":"2023042709452564000_2023.04.24.538119v1.28","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.neuron.2021.01.015","article-title":"Cochlear neural degeneration disrupts hearing in background noise by increasing auditory cortex internal noise","volume":"109","year":"2021","journal-title":"Neuron"},{"key":"2023042709452564000_2023.04.24.538119v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(89)90115-9"},{"key":"2023042709452564000_2023.04.24.538119v1.30","doi-asserted-by":"publisher","DOI":"10.1177\/00034894931020S101"},{"key":"2023042709452564000_2023.04.24.538119v1.31","first-page":"286","article-title":"Otoacoustic Estimates of Cochlear Tuning: Testing Predictions in Macaque","volume":"1403","year":"2011","journal-title":"AIP Conf Proc"},{"key":"2023042709452564000_2023.04.24.538119v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(95)00184-0"},{"key":"2023042709452564000_2023.04.24.538119v1.33","doi-asserted-by":"crossref","first-page":"729625","DOI":"10.3389\/fnmol.2021.729625","article-title":"LGR5-Positive Supporting Cells Survive Ototoxic Trauma in the Adult Mouse Cochlea","volume":"14","year":"2021","journal-title":"Front Mol Neurosci"},{"key":"2023042709452564000_2023.04.24.538119v1.34","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-004-5050-1"},{"key":"2023042709452564000_2023.04.24.538119v1.35","first-page":"1","article-title":"Retrograde cochlear neuronal degeneration in human subjects","volume":"450","year":"1988","journal-title":"Acta Otolaryngol Suppl"},{"key":"2023042709452564000_2023.04.24.538119v1.36","doi-asserted-by":"publisher","DOI":"10.3109\/00206099209072917"},{"key":"2023042709452564000_2023.04.24.538119v1.37","doi-asserted-by":"crossref","unstructured":"Taylor, R. R. , D. J. Jagger and A. Forge (2012). \u201cDefining the cellular environment in the organ of Corti following extensive hair cell loss: a basis for future sensory cell replacement in the Cochlea.\u201d PLoS One 7(1):p e30577.","DOI":"10.1371\/journal.pone.0030577"},{"key":"2023042709452564000_2023.04.24.538119v1.38","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19970505)381:2<188::AID-CNE6>3.0.CO;2-#"},{"key":"2023042709452564000_2023.04.24.538119v1.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-17-05466.1996"},{"key":"2023042709452564000_2023.04.24.538119v1.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0937-20.2020"},{"key":"2023042709452564000_2023.04.24.538119v1.41","doi-asserted-by":"crossref","unstructured":"Wu, P. Z. , W. P. Wen , J. T. O\u2019Malley and M. C. Liberman (2019). \u201cAssessing fractional hair cell survival in archival human temporal bones.\u201d Laryngoscope.","DOI":"10.1002\/lary.27991"},{"key":"2023042709452564000_2023.04.24.538119v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(93)90159-X"},{"key":"2023042709452564000_2023.04.24.538119v1.43","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4678-11.2012"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.04.24.538119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:35:06Z","timestamp":1768451706000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.04.24.538119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,24]]},"references-count":43,"URL":"https:\/\/doi.org\/10.1101\/2023.04.24.538119","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.heares.2023.108815","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,4,24]]},"subtype":"preprint"}}