{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:16:49Z","timestamp":1788430609646,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Primary adrenal insufficiency is a life\u2010threatening disorder, which requires lifelong hormone replacement therapy. Transplantation of xenogeneic adrenal cells is a potential alternative approach for the treatment of adrenal insufficiency. For a successful outcome of this replacement therapy, transplanted cells should provide adequate hormone secretion and respond to adrenal physiological stimuli. Here, we describe the generation and characterization of primary porcine adrenal spheroids capable of replacing the function of adrenal glands in vivo. Cells within the spheroids morphologically resembled adult adrenocortical cells and synthesized and secreted adrenal steroid hormones in a regulated manner. Moreover, the embedding of the spheroids in alginate led to the formation of cellular elongations of steroidogenic cells migrating centripetally towards the inner part of the slab, similar to zona Fasciculata cells in the intact organ. Finally, transplantation of adrenal spheroids in adrenalectomized SCID mice reversed the adrenal insufficiency phenotype, which significantly improved animals\u2019 survival. Overall, such adrenal models could be employed for disease modeling and drug testing, and represent the first step toward potential clinical trials in the future.<\/jats:p>","DOI":"10.1111\/xen.12819","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T08:56:20Z","timestamp":1691398580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transplantation of porcine adrenal spheroids for the treatment of adrenal insufficiency"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6966-0521","authenticated-orcid":false,"given":"Maria","family":"Malyukov","sequence":"first","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeny","family":"Gelfgat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Ruiz\u2010Babot","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susann","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giatgen","family":"Spinas","sequence":"additional","affiliation":[{"name":"Medical Faculty University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Diabetology and Clinical Nutrition University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"},{"name":"Department of Endocrinology Diabetology and Clinical Nutrition University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Reisch","sequence":"additional","affiliation":[{"name":"Medizinische Klinik IV Klinikum der Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Nawroth","sequence":"additional","affiliation":[{"name":"Medical Faculty Heidelberg University Hospital Heidelberg Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan R.","family":"Bornstein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"},{"name":"Faculty of Life Sciences &amp; Medicine School of Cardiovascular and Metabolic Medicine and Sciences King's College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9635-4860","authenticated-orcid":false,"given":"Charlotte","family":"Steenblock","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Ludwig","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III University Hospital Carl Gustav Carus Technical University Dresden Dresden Germany"},{"name":"Department of Endocrinology Diabetology and Clinical Nutrition University Hospital Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Hospital Carl Gustav Carus of TU Dresden Faculty of Medicine Dresden Germany"},{"name":"DFG\u2010Center for Regenerative Therapies Dresden Technical University Dresden Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2017.10.010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000486004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2014.08.008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010022\u201003070\u20103"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/09636897211000014"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010020\u201002107\u20106"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120627"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/71894"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0303\u20107207(99)00070\u20102"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1500242112"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c130050"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194643"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.11.001"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE\u201017\u20100563"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1191"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/xen.12595"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2014.10.006"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091\u2010679X(10)96017\u20102"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102020\u2010321339"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.25.2.407"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041450110"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201005096\u2010x"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194643"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0997\u2010978"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coemr.2019.07.009"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1814072115"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010021\u201000491\u20104"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2016.0877"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200700228"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2012.12.003"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00238"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0300\u20109629(84)90597\u20108"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960\u20100760(03)00212\u20107"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2017\u201000505"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfa.2015.01.027"}],"container-title":["Xenotransplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/xen.12819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T06:45:28Z","timestamp":1695365128000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/xen.12819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,7]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/xen.12819"],"URL":"https:\/\/doi.org\/10.1111\/xen.12819","archive":["Portico"],"relation":{},"ISSN":["0908-665X","1399-3089"],"issn-type":[{"value":"0908-665X","type":"print"},{"value":"1399-3089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,7]]},"assertion":[{"value":"2023-03-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12819"}}