{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T15:44:10Z","timestamp":1764603850947,"version":"3.40.5"},"reference-count":17,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BC Transplant Research Foundation"},{"name":"Sernova Corp"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>This study aimed to investigate the survival and efficacy indicators of human thyroid tissue transplantation into a retrievable, prevascularized implanted Sernova Corp Cell Pouch\u2122 (CP) device. Thyroid tissue from human donors was transplanted subcutaneously into the pre-implanted CP device or into the subcutaneous (SC) space alone as a control in a nude <jats:italic>Mus musculus<\/jats:italic> model. Transplanted <jats:italic>M<\/jats:italic>. <jats:italic>musculus<\/jats:italic> were monitored for human serum thyroglobulin (TG) levels for 3 months until the transplants were removed for histological assessment. Human thyroid tissue survived and continued to produce TG in transplanted nude <jats:italic>M<\/jats:italic>. <jats:italic>musculus<\/jats:italic> in the CP, with no adverse events. CP transplants exhibited more persistent and robust production of human TG than tissue placed in the SC space alone from 3 to 13 weeks post transplantation. Fresh thyroid transplants had better survival and function compared to cryopreserved transplants. Thyroid transplant viability correlated with TG levels at 3 months post-transplant (p = 0.03). Immunofluorescence staining of transplants for TG and TPO localized in thyroid follicles. Human thyroid tissue transplanted into the subcutaneously implanted pre-vascularized CP in nude <jats:italic>M<\/jats:italic>. <jats:italic>musculus<\/jats:italic> survived and continued to produce robust and persistent human TG and warrants further investigation as a treatment for postoperative hypothyroidism.<\/jats:p>","DOI":"10.1371\/journal.pone.0262345","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T18:31:37Z","timestamp":1642703497000},"page":"e0262345","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Subcutaneous transplantation of human thyroid tissue into a pre-vascularized Cell Pouch\u2122 device in a Mus musculus model: Evidence of viability and function for thyroid transplantation"],"prefix":"10.1371","volume":"17","author":[{"given":"Sam M.","family":"Wiseman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arash","family":"Memarnejadian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guilaine K.","family":"Boyce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-7317","authenticated-orcid":true,"given":"Anne","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blair A.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel T.","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian D.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delfina M.","family":"Mazzuca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip M.","family":"Toleikis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"pone.0262345.ref001","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/S0140-6736(17)30703-1","article-title":"Hypothyroidism","volume":"390","author":"L Chaker","year":"2017","journal-title":"Lancet"},{"key":"pone.0262345.ref002","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1258\/jrsm.2010.10k052","article-title":"The discovery of thyroid replacement therapy. Part 3: A complete transformation","volume":"104","author":"S. Slater","year":"2011","journal-title":"J R Soc Med."},{"key":"pone.0262345.ref003","doi-asserted-by":"crossref","first-page":"289","DOI":"10.21053\/ceo.2016.01578","article-title":"Review of heterotopic thyroid autotransplantation","volume":"10","author":"M Sakr","year":"2017","journal-title":"Clin Exp Otorhinolaryngol"},{"key":"pone.0262345.ref004","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s00423-018-1654-5","article-title":"Parathyroid autotransplantation in thyroid surgery","volume":"403","author":"A Sitges-Serra","year":"2018","journal-title":"Langenbeck\u2019s Arch Surg"},{"key":"pone.0262345.ref005","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1097\/TP.0000000000000864","article-title":"Diabetes is reversed in a murine model by marginal mass syngeneic islet transplantation using a subcutaneous cell pouch device","volume":"99","author":"AR Pepper","year":"2015","journal-title":"Transplantation"},{"key":"pone.0262345.ref006","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.acthis.2018.02.005","article-title":"Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives","volume":"120","author":"JC Stockert","year":"2018","journal-title":"Acta Histochem"},{"key":"pone.0262345.ref007","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1210\/jc.2012-1063","article-title":"Risk of hypothyroidism following hemithyroidectomy: Systematic review and meta-analysis of prognostic studies","volume":"97","author":"H Verloop","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"pone.0262345.ref008","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1089\/thy.2012.0205","article-title":"Clinical practice guidelines for hypothyroidism in adults: Cosponsored by the American Association of clinical endocrinologists and the American Thyroid Association","volume":"22","author":"JR Garber","year":"2012","journal-title":"Thyroid"},{"key":"pone.0262345.ref009","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1089\/thy.2014.0028","article-title":"Guidelines for the treatment of hypothyroidism: Prepared by the American thyroid association task force on thyroid hormone replacement","volume":"24","author":"J Jonklaas","year":"2014","journal-title":"Thyroid"},{"key":"pone.0262345.ref010","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000339444","article-title":"2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism","volume":"1","author":"WM Wiersinga","year":"2012","journal-title":"Eur Thyroid J"},{"key":"pone.0262345.ref011","first-page":"265","article-title":"Diretrizes cl\u00ednicas pr\u00e1ticas para o manejo do hipotiroidismo","volume":"57","author":"G Brenta","year":"2013","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"pone.0262345.ref012","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s12020-016-1199-8","article-title":"The emergence of levothyroxine as a treatment for hypothyroidism","volume":"55","author":"V. Hennessey J","year":"2017","journal-title":"Endocrine"},{"key":"pone.0262345.ref013","doi-asserted-by":"crossref","first-page":"e22552","DOI":"10.1371\/journal.pone.0022552","article-title":"Levothyroxine Monotherapy Cannot Guarantee Euthyroidism in All Athyreotic Patients","volume":"6","author":"D Gullo","year":"2011","journal-title":"PLoS One"},{"key":"pone.0262345.ref014","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1089\/thy.2017.0681","article-title":"An online survey of hypothyroid patients demonstrates prominent dissatisfaction","volume":"28","author":"SJ Peterson","year":"2018","journal-title":"Thyroid"},{"key":"pone.0262345.ref015","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.stem.2015.09.004","article-title":"Regeneration of Thyroid Function by Transplantation of Differentiated Pluripotent Stem Cells","volume":"17","author":"AA Kurmann","year":"2015","journal-title":"Cell Stem Cell"},{"key":"pone.0262345.ref016","doi-asserted-by":"crossref","first-page":"034105","DOI":"10.1088\/1758-5090\/aa7fdd","article-title":"Bioprinting of a functional vascularized mouse thyroid gland construct","volume":"9","author":"EA Bulanova","year":"2017","journal-title":"Biofabrication"},{"key":"pone.0262345.ref017","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.mce.2017.01.038","article-title":"Thyroid hormone biosynthesis and release","volume":"458","author":"DP Carvalho","year":"2017","journal-title":"Mol Cell Endocrinol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T18:31:58Z","timestamp":1642703518000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0262345"}},"subtitle":[],"editor":[{"given":"Oded","family":"Cohen","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0262345","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2022,1,20]]}}}