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Sheep represent a valuable in\u00a0vivo and ex\u00a0vivo model for IVDD due to their anatomical and biomechanical similarities with humans and the possibility to access disc samples at early stages of degeneration. In\u00a0vitro, isolated annulus fibrosus (AF) and nucleus pulposus (NP) cells may provide insights into age\u2010associated degenerative processes; this work investigates how well they capture senescence and metabolic alterations observed in\u00a0vivo. Transcriptomic profiling of AF and NP cells from healthy young lambs and mildly degenerated aged sheep revealed distinct age\u2010 and tissue\u2010specific signatures, with upregulation of inflammatory mediators, ECM\u2010remodelling enzymes, and senescence\u2010associated genes in aged cells. Cross\u2010species deconvolution using a human single\u2010cell RNA\u2010sequencing reference confirmed conserved transcriptional modules between aged sheep and human degenerated discs, underscoring the model's translational relevance. However, functional assays demonstrated comparable responses of young and aged cells under basal conditions and after exposure to pro\u2010degenerative stressors (IL\u20101\u03b2, senescence induction). Altogether, these findings validate sheep cells as a suitable in\u00a0vitro model for studying disc degeneration mechanisms and for preclinical testing, although aged donors offer no clear additional functional benefits.<\/jats:p>","DOI":"10.1111\/jcmm.71026","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T13:02:08Z","timestamp":1769086928000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic and Functional Comparison of Cells Isolated From Healthy and Degenerated Ovine Intervertebral Discs"],"prefix":"10.1111","volume":"30","author":[{"given":"Paul","family":"Humbert","sequence":"first","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Danet","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma\u00eblle","family":"Carrot","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floriane","family":"Etienne","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"},{"name":"Department of Diagnostic Imaging CRIP, ONIRIS, College of Veterinary Medicine, Food Science and Engineering  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Halgand","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Vinatier","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9r\u00f4me","family":"Guicheux","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Fusellier","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"},{"name":"Department of Diagnostic Imaging CRIP, ONIRIS, College of Veterinary Medicine, Food Science and Engineering  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1816-1649","authenticated-orcid":false,"given":"Catherine","family":"Le Visage","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Romain","family":"Guiho","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, Oniris, CHU Nantes, INSERM, Regenerative Medicine and Skeleton, RMeS, UMR 1229  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00733-9"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00098-X"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"1","article-title":"Painful Intervertebral Disc Degeneration and Inflammation: From Laboratory Evidence to Clinical Interventions","volume":"9","author":"Lyu F. 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