{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:34:22Z","timestamp":1760056462802,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S015167\/1"],"award-info":[{"award-number":["MR\/S015167\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Allogeneic chondrocyte therapies present an attractive alternative to existing autologous therapies for the repair of cartilage defects, enabling the selection of optimal donor cells and streamlined manufacturing processes. This study investigates the potential of juvenile chondrocytes derived from human infantile (aged 0\u20134 y) polydactyly digits and the iliac apophysis for cartilage repair using Good Manufacturing Practice bioreactor expansion. Iliac apophysis (n = 4) and polydactyly tissues (n = 4) were assessed histologically. Chondrocytes were isolated enzymatically and cultured using standard tissue culture plastic (TCP) methodology. Upon sufficient cell expansion, chondrocytes were seeded into the Quantum\u00ae bioreactor system or onto TCP (\u00b1vitronectin coating). The manufactured chondrocytes growth rates, total cell yields, chondrogenic pellet forming capacity (GAG\/DNA, histology), immunoprofiles (flow cytometry) and gene expression (RT-qPCR) were assessed. Equivalent chondrocyte numbers were isolated from polydactyly and iliac apophysis donors per wet weight of tissue. Quantum\u00ae-expanded chondrocytes from both sources yielded comparable cell numbers; however, growth was slowed in the Quantum\u00ae compared to TCP. Polydactyly and iliac apophysis-derived chondrocytes expressed chondrocyte cell surface markers (CD166, CD44, CD151, SOX9) and formed chondrogenic pellets. Quantum\u00ae bioreactor expansion did not alter, gene expression or capacity to form glycosaminoglycans (GAGs (normalised to DNA content)) compared to matched TCP expansion. Juvenile cartilage donors are a promising chondrocyte source for the development of an allogeneic therapy. This novel study expanding juvenile chondrocytes in the Quantum\u00ae GMP-compliant bioreactor suggests that culture conditions may need modification to improve growth, whilst retaining cartilage forming capacity.<\/jats:p>","DOI":"10.3390\/ijms26199566","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9566","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developing Up-Scale Allogeneic Chondrocyte Therapies Using Juvenile Donor Cartilage"],"prefix":"10.3390","volume":"26","author":[{"given":"Charlotte H.","family":"Hulme","sequence":"first","affiliation":[{"name":"Centre for Regenerative Medicine Research, School of Life Sciences, Keele University, Keele, Stoke-on-Trent ST5 5BG, Staffordshire, UK"},{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5953-1389","authenticated-orcid":false,"given":"Jade","family":"Perry","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine Research, School of Life Sciences, Keele University, Keele, Stoke-on-Trent ST5 5BG, Staffordshire, UK"},{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9534-7565","authenticated-orcid":false,"given":"Helen S.","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine Research, School of Life Sciences, Keele University, Keele, Stoke-on-Trent ST5 5BG, Staffordshire, UK"},{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Lan","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine Research, School of Life Sciences, Keele University, Keele, Stoke-on-Trent ST5 5BG, Staffordshire, UK"},{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thavisha","family":"Ranasinghe","sequence":"additional","affiliation":[{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Kiely","sequence":"additional","affiliation":[{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Freeman","sequence":"additional","affiliation":[{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6055-648X","authenticated-orcid":false,"given":"Jonathan","family":"Wright","sequence":"additional","affiliation":[{"name":"Limb Reconstruction Unit, Royal National Orthopaedic Hospital, Stanmore, London HA7 4LP, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina T.","family":"Wright","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine Research, School of Life Sciences, Keele University, Keele, Stoke-on-Trent ST5 5BG, Staffordshire, UK"},{"name":"Oswestry Keele Orthopaedic Research Group, Robert Jones and Agnes Hunt Orthopaedic Hospital Foundation Trust, Oswestry SY10 7AG, Shropshire, UK"},{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Birmingham B15 2GW, West Midlands, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41584-023-00979-5","article-title":"Failure of Cartilage Regeneration: Emerging Hypotheses and Related Therapeutic Strategies","volume":"19","author":"Muthu","year":"2023","journal-title":"Nat. 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