{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T13:31:14Z","timestamp":1783431074671,"version":"3.54.6"},"reference-count":87,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Patients suffering from microtia have limited treatment options for auricular reconstruction due to donor-site morbidity, complications, and unaesthetic outcome. Therefore, tissue engineering emerged as an alternative therapeutic option. Here, we generated and characterized human auricular cartilage using differentiated human adipose mesenchymal stem cells (hASCs) combined with human auricular chondrocytes.<\/jats:p>\n               <jats:p>The differentiated hASCs were analysed for their morphology, phenotype, gene, and protein expression of chondrogenic markers, and biochemical composition at different time points in 2D and 3D\u00a0in vitro. Importantly, we improved conditions for chondrogenic differentiation of hASCs\u00a0in vitro\u00a0to enhance their proliferation, survival, and deposition of cartilaginous-matrix proteins. In particular, gene expression analysis revealed an upregulation of cartilage oligomeric matrix protein (COMP) and aggrecan core protein (ACAN) in hASCs using the improved differentiation protocol\u00a0in vitro.<\/jats:p>\n               <jats:p>Additionally, we observed that co-seeding of hASCs with chondrocytes in a 1:5 ratio significantly enhanced the de novo\u00a0auricular cartilage formation in a collagen-I bioink after 8 weeks on immunodeficient rat. In particular, the co-culture resulted in reduced shrinkage, and increased cartilage matrix production as confirmed by GAG deposition in vivo. Our results demonstrate that in co-cultures, hASCs stimulate cartilage formation due to a synergistic effect: hASCs\u2019 differentiation into chondrocytes and a trophic effect of hASCs on human auricular chondrocytes.<\/jats:p>\n               <jats:p>Here we demonstrate the successful use of an hASC-chondrocyte co-culture technique for auricular cartilage tissue engineering in 3D collagen-I bioink. This co-culture approach omits the major drawbacks of traditional cartilage transplantation and thus, represents a fundamental step towards clinical translation.<\/jats:p>","DOI":"10.1093\/stcltm\/szae098","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T10:56:49Z","timestamp":1746010609000},"source":"Crossref","is-referenced-by-count":3,"title":["Adipose-mesenchymal stem cells enhance the formation of auricular cartilage in vitro\u00a0and in vivo"],"prefix":"10.1093","volume":"14","author":[{"given":"Dominika","family":"Zielinska","sequence":"first","affiliation":[{"name":"Tissue Biology Research Unit, Department of Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Medical Faculty,\u00a0University of Zurich , 8006\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Micka-Michalak","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, Department of Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Medical Faculty,\u00a0University of Zurich , 8006\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyrije","family":"Ademi","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, Department of Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Medical Faculty,\u00a0University of Zurich , 8006\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Fisch","sequence":"additional","affiliation":[{"name":"Tissue Engineering and Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zurich, 8093\u00a0Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Boeni","sequence":"additional","affiliation":[{"name":"White House Centre for Liposuction , 8044\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Linder","sequence":"additional","affiliation":[{"name":"Otorhinolaryngology Clinic, Cantonal Hospital Luzern , 6000\u00a0 Luzern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ueli","family":"Moehrlen","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, Department of Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Medical Faculty,\u00a0University of Zurich , 8006\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Department of Pediatric Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Biedermann","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, Department of Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Medical Faculty,\u00a0University of Zurich , 8006\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes S","family":"Klar","sequence":"additional","affiliation":[{"name":"Tissue Biology Research Unit, Department of Surgery, University Children\u2019s Hospital Zurich, University of Zurich , 8952 Schlieren ,","place":["Switzerland"]},{"name":"Medical Faculty,\u00a0University of Zurich , 8006\u00a0 Zurich ,","place":["Switzerland"]},{"name":"Children\u2019s Research Center, University Children\u2019s Hospital Zurich , 8008\u00a0 Zurich ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025043006564286600_CIT0001","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13287-015-0273-0","article-title":"Combining regenerative medicine strategies to provide durable reconstructive options: auricular cartilage tissue 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