{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:57:20Z","timestamp":1787497040687,"version":"build-2736575974"},"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003354","name":"Garnett Passe and Rodney Williams Memorial Foundation","doi-asserted-by":"publisher","award":["2023_ASSF_Creber"],"award-info":[{"award-number":["2023_ASSF_Creber"]}],"id":[{"id":"10.13039\/501100003354","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203312*"],"award-info":[{"award-number":["NIHR203312*"]}],"id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rinri Therapeutics Ltd"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Hearing loss is a significant health burden across all stages of life. One in 5 people suffer hearing loss, with 5% of the world\u2019s population experiencing disabling hearing loss. A large proportion of this loss is the consequence of damage or loss of neurosensory structures, termed \u201csensorineural\u201d hearing loss. A recent advance in the treatment of sensorineural hearing loss has occurred, with the advent of inner ear stem cell therapy. Focus has pivoted from augmenting existing neural structures to regenerating neural frameworks. To date, stem cell therapy is limited by the host immune system and rejection of donor cells. A better understanding of immunity in the inner is ear required to progress stem cell therapy for hearing loss. This review outlines a contemporary understanding of the inner ear immune system. We discuss concepts of immune dysregulation that may lead to common inner ear pathologies, and, in doing so, review the efficacy of current pharmacotherapies that mitigate end organ damage through a process of immunosuppression. Current literature is appraised through a systematic review exploring two areas of focus; immunosuppression therapies for the treatment of inner ear pathology associated immune dysregulation, and, subsequently, the efficacy of immunosuppressive agents in translational models of inner ear stem cell therapy. Through greater understanding of these concepts, and systematic appraisal of the literature, this review summarises the literature for contemporary immunosuppressive regimes that may facilitate stem cell accommodation in the cochlea and auditory nerve.<\/jats:p>","DOI":"10.1371\/journal.pone.0318165","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T13:42:52Z","timestamp":1739454172000},"page":"e0318165","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Current and emerging approaches to cochlear immunosuppression with translation to human inner ear stem cell therapy: A systematic review"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-3371","authenticated-orcid":true,"given":"Nathan J.","family":"Creber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3065-0269","authenticated-orcid":true,"given":"Jameel","family":"Muzaffar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shravan","family":"Gowrishankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Borsetto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Phillips","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8147-1549","authenticated-orcid":true,"given":"Matthew E.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"pone.0318165.ref001","unstructured":"Geneva: World Health Organization. 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the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results","volume":"49","author":"LCM Barboza","year":"2016","journal-title":"Braz J Med Biol Res"},{"issue":"1","key":"pone.0318165.ref046","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s13287-018-0967-1","article-title":"Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea","volume":"9","author":"J Chen","year":"2018","journal-title":"Stem Cell Res Ther"},{"key":"pone.0318165.ref047","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.heares.2018.06.015","article-title":"Microenvironmental support for cell delivery to the inner ear","volume":"368","author":"J Schulze","year":"2018","journal-title":"Hear Res"},{"issue":"6","key":"pone.0318165.ref048","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.ymthe.2019.03.018","article-title":"Engraftment of Human Stem Cell-Derived Otic Progenitors in the Damaged Cochlea","volume":"27","author":"A Lopez-Juarez","year":"2019","journal-title":"Mol Ther"},{"issue":"6","key":"pone.0318165.ref049","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.3390\/jcm9061711","article-title":"Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration","volume":"9","author":"AA Eshraghi","year":"2020","journal-title":"J Clin Med"},{"key":"pone.0318165.ref050","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.actbio.2020.03.007","article-title":"An engineered three-dimensional stem cell niche in the inner ear by applying a nanofibrillar cellulose hydrogel with a sustained-release neurotrophic factor delivery system","volume":"108","author":"HT Chang","year":"2020","journal-title":"Acta Biomater"},{"issue":"2","key":"pone.0318165.ref051","first-page":"167","article-title":"Otolaryngology Section, University of Padova, Padova, Italy, Franz L, Frosolini A, Department of Neuroscience DNS, Audiology Unit, University of Padova, Treviso, Italy, Parrino D, Department of Neuroscience DNS, Audiology Unit, University of Padova, Treviso, Italy, et al. Ototoxicity of Immunosuppressant Drugs: A Systematic Review","volume":"18","author":"Department of Neuroscience DNS","year":"2022","journal-title":"Int Adv Otol"},{"key":"pone.0318165.ref052","doi-asserted-by":"crossref","first-page":"593917","DOI":"10.3389\/fneur.2020.593917","article-title":"Is Cyclosporine Ototoxic?","volume":"11","author":"S. Waissbluth","year":"2020","journal-title":"Front Neurol"},{"issue":"11","key":"pone.0318165.ref053","doi-asserted-by":"crossref","first-page":"e54","DOI":"10.1038\/emm.2013.94","article-title":"Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine","volume":"45","author":"MB Murphy","year":"2013","journal-title":"Exp Mol Med"},{"issue":"9","key":"pone.0318165.ref054","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.1182\/blood-2002-07-2104","article-title":"Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide","volume":"101","author":"M Krampera","year":"2003","journal-title":"Blood"},{"issue":"3","key":"pone.0318165.ref055","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1097\/01.TP.0000045055.63901.A9","article-title":"Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation","volume":"75","author":"WT Tse","year":"2003","journal-title":"Transplantation"},{"key":"pone.0318165.ref056","article-title":"Characterization of different immune suppression approaches for intracochlear transplantation of human induced pluripotent stem-cell derived otic progenitor cells in the Mongolian gerbil","volume":"101","author":"Hartmann MK Angeliki","year":"2022","journal-title":"Laryngorhinootologie [Internet]"},{"issue":"3","key":"pone.0318165.ref057","doi-asserted-by":"crossref","first-page":"e810","DOI":"10.1097\/MJT.0000000000000150","article-title":"Tacrolimus Versus Cyclosporine as Primary Immunosuppressant After Renal Transplantation: A Meta-Analysis and Economics Evaluation","volume":"23","author":"J yu Liu","year":"2016","journal-title":"American Journal of Therapeutics"},{"key":"pone.0318165.ref058","article-title":"Tacrolimus versus cyclosporin as primary immunosuppression for kidney transplant recipients. Cochrane Kidney and Transplant Group, editor","author":"AC Webster","year":"2005","journal-title":"Cochrane Database of Systematic Reviews [Internet]"},{"issue":"1","key":"pone.0318165.ref059","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/s42003-021-02237-4","article-title":"Immunological considerations and challenges for regenerative cellular therapies","volume":"4","author":"S Petrus-Reurer","year":"2021","journal-title":"Commun Biol"},{"key":"pone.0318165.ref060","unstructured":"Salt AN. https:\/\/tech.wustl.edu\/tech-summary\/cochlear-fluids-simulator\/. Last accessed 27th February 2023."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T13:43:19Z","timestamp":1739454199000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318165"}},"subtitle":[],"editor":[{"given":"Annalisa","family":"Pace","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,13]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0318165","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,13]]}}}