{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T15:41:15Z","timestamp":1768318875559,"version":"3.49.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T00:00:00Z","timestamp":1536710400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Mayo Clinic ENT Regenerative Medicine Program"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Objectives\/Hypothesis<\/jats:title><jats:p>Vocal fold (VF) paralysis by sectioning the recurrent laryngeal nerve dramatically impacts the life of thyroidectomy patients. Volume\u2010expanding materials can temporarily restore VF medialization. To prolong this benefit, adipose mesenchymal stem cells (ADSCs) and micronized acellular dermis (MACD) were co\u2010injected in a rabbit model of injection medialization laryngoplasty. Biomarkers of in situ proliferation were identified by mass spectrometry proteomics and pathway analysis to guide future efforts to increase the length of benefit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ADSCs were expanded and\/or differentiated into chondrocytes (CHON) as collagen microspheres. After VF paralysis rabbits received MACD, MACD\u2009+\u2009undifferentiated ADSC, or MACD+CHON, ADSCs differentiated into chondrocytes. After 12 weeks, animals were sacrificed and 5\u2010\u00b5m paraffin\u2010embedded cryosections were prepared from larynges for hematoxylin and eosin visualization and nanoflow liquid chromatography electrospray\u2010ionization tandem\u2010mass spectrometry analysis of tissue collections. Validated proteins were processed by Venn subtraction and gene ontology (GO) overrepresentation analysis to identify unique pathways and biomarkers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Confirmed proteins numbered 147 (MACD), 1,243 (MACD+ADSC), and 1,033 (MACD+CHON). Totally, 333 proteins were uniquely found in the MACD+ADSC group, including mesenchymal surface markers CD9, CD44, fibronectin, and vimentin. Over 70% of proteins belonged to catalytic activity and binding GO categories, with the histone (H) family being overrepresented (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). Histone variants H3.3, H2A.V, and H2A.Z (associated with open chromatin states) were overrepresented in the MACD+ADSC group, whereas structural histones H2A, H2B, and H4 were not.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Biomarkers, including atypical histones, are associated with in vivo proliferation of ADSCs and an expanded VF medialization volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 128:E402\u2013E408, 2018<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.27429","type":"journal-article","created":{"date-parts":[[2018,9,12]],"date-time":"2018-09-12T19:00:32Z","timestamp":1536778832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Histone Variants as Stem Cell Biomarkers for Long\u2010Term Injection Medialization Laryngoplasty"],"prefix":"10.1002","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8010-961X","authenticated-orcid":false,"given":"Stephen","family":"Voss","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Medical Genome Facility\u2010Proteomics, Mayo Clinic  Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serban","family":"San\u2010Marina","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Medical Genome Facility\u2010Proteomics, Mayo Clinic  Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5419-7748","authenticated-orcid":false,"given":"Michael S.","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Otolaryngology\u2013Head and Neck Surgery, Prevea Health Services  Green Bay Wisconsin U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8770-8463","authenticated-orcid":false,"given":"Dale","family":"Ekbom","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Medical Genome Facility\u2010Proteomics, Mayo Clinic  Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Madden","sequence":"additional","affiliation":[{"name":"Medical Genome Facility\u2010Proteomics, Mayo Clinic  Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Cristine","family":"Charlesworth","sequence":"additional","affiliation":[{"name":"Medical Genome Facility\u2010Proteomics, Mayo Clinic  Rochester Minnesota"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey R.","family":"Janus","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Medical Genome Facility\u2010Proteomics, Mayo 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