{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:22:32Z","timestamp":1760059352106,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo de Investigaciones Sanitarias","award":["PI19\/01788","2021-SGR-00877","RD21\/0017\/0022"],"award-info":[{"award-number":["PI19\/01788","2021-SGR-00877","RD21\/0017\/0022"]}]},{"name":"Generalitat de Catalunya","award":["PI19\/01788","2021-SGR-00877","RD21\/0017\/0022"],"award-info":[{"award-number":["PI19\/01788","2021-SGR-00877","RD21\/0017\/0022"]}]},{"name":"ISCIII","award":["PI19\/01788","2021-SGR-00877","RD21\/0017\/0022"],"award-info":[{"award-number":["PI19\/01788","2021-SGR-00877","RD21\/0017\/0022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Secondary osteonecrosis (ON) is a common complication in paediatric cancer survivors. Combining multipotent mesenchymal stromal cells (MSCs) with core decompression surgery halts disease progression and stimulates bone regeneration. However, the success of advanced therapy medicinal products (ATMPs) requires versatile \u201coff-the-shelf\u201d tissue engineering products (TEPs). This study evaluated the safety and efficacy of TEPs loaded with allogeneic MSCs from Wharton\u2019s jelly (WJ-MSCs) in a large-animal model of bone regeneration to support a paediatric investigational plan for ON patients. WJ-MSC-laden fibrin-based hydrogels combined with a synthetic bone substitute (PRO-DENSETM) were tested in 16 juvenile sheep (8 males and 8 females) distributed in four experimental groups. Each animal received four cylindrical bone defects in the femoral and tibial epiphyses and was assessed at 6 and 12 weeks. Safety was confirmed, and bone regeneration was observed across all groups. A combination of WJ-MSCs with PRO-DENSETM led to improved histological scores, osteogenesis, and construct integration. Trabecular bone volume also increased more in cellular groups over time. However, effects were inconsistent across groups, reflecting the variability seen in clinical trials and highlighting the significant impact of factors such as immunogenetic compatibility, MSC batch potency, and interaction with the recipient\u2019s microenvironment on the therapeutic effectiveness and successful clinical translation of allogeneic ATMPs.<\/jats:p>","DOI":"10.3390\/cells14120862","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:13:01Z","timestamp":1749460381000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical Assessment in Juvenile Sheep of an Allogeneic Bone Tissue Engineering Product with Wharton\u2019s Jelly Mesenchymal Stromal Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4858-0142","authenticated-orcid":false,"given":"Raquel","family":"Cabrera-P\u00e9rez","sequence":"first","affiliation":[{"name":"Bioprocessing for Advanced Cell Therapies (BACT) Group, Cell Therapy Service, Blood and Tissue Bank (BST), 08005 Barcelona, Catalonia, Spain"},{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Carreras-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Bioprocessing for Advanced Cell Therapies (BACT) Group, Cell Therapy Service, Blood and Tissue Bank (BST), 08005 Barcelona, Catalonia, Spain"},{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00c1ngela","family":"Roig-Molina","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-0294","authenticated-orcid":false,"given":"Alba","family":"L\u00f3pez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Bioprocessing for Advanced Cell Therapies (BACT) Group, Cell Therapy Service, Blood and Tissue Bank (BST), 08005 Barcelona, Catalonia, Spain"},{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0661-441X","authenticated-orcid":false,"given":"Irene","family":"Portas-Torres","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Batlle-Morera","sequence":"additional","affiliation":[{"name":"Tissue Engineering Unit, Centre for Genomic Regulation (CRG), Barcelona Biomedical Research Park (PRBB), 08003 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"V\u00e9lez","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"},{"name":"Musculoskeletal Tumour Unit and Orthopaedic Surgery Department, Vall d\u2019Hebron University Hospital (HUVH), 08035 Barcelona, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9719-5235","authenticated-orcid":false,"given":"Joaquim","family":"Vives","sequence":"additional","affiliation":[{"name":"Bioprocessing for Advanced Cell Therapies (BACT) Group, Cell Therapy Service, Blood and Tissue Bank (BST), 08005 Barcelona, Catalonia, Spain"},{"name":"Musculoskeletal Tissue Engineering Group, Vall d\u2019Hebron Research Institute (VHIR) and Universitat Aut\u00f2noma de Barcelona (UAB), 08035 Barcelona, Catalonia, Spain"},{"name":"Medicine Department, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Catalonia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","unstructured":"(2023, November 21). 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