{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:54:06Z","timestamp":1789052046965,"version":"build-2803163510"},"reference-count":85,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T00:00:00Z","timestamp":1726790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["esskajournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Knee surg. sports traumatol. arthrosc."],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>This systematic review aimed to investigate in animal models the presence of disease\u2010modifying effects driven by non\u2010bone marrow\u2010derived and non\u2010adipose\u2010derived products, with a particular focus on umbilical cord and placenta\u2010derived cell\u2010based therapies for the intra\u2010articular injective treatment of osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review was performed on three electronic databases (PubMed, Web of Science and Embase) according to PRISMA guidelines. The results were synthesised to investigate disease\u2010modifying effects in preclinical animal studies comparing injectable umbilical cord, placenta, and other sources\u2010derived products with OA controls. The risk of bias was assessed using the SYRCLE tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 80 studies were included (2314 animals). Cell therapies were most commonly obtained from the umbilical cord in 33 studies and placenta\/amniotic tissue in 18. Cell products were xenogeneic in 61 studies and allogeneic in the remaining 19 studies. Overall, 25\/27 (92.6%) of studies on umbilical cord\u2010derived products documented better results compared to OA controls in at least one of the following outcomes: macroscopic, histological and\/or immunohistochemical findings, with 19\/22 of studies (83.4%) show positive results at the cartilage level and 4\/6 of studies (66.7%) at the synovial level. Placenta\u2010derived injectable products documented positive results in 13\/16 (81.3%) of the studies, 12\/15 (80.0%) at the cartilage level, and 2\/4 (50.0%) at the synovial level, but 2\/16 studies (12.5%) found overall worse results than OA controls. Other sources (embryonic, synovial, peripheral blood, dental pulp, cartilage, meniscus and muscle\u2010derived products) were investigated in fewer preclinical studies. The risk of bias was low in 42% of items, unclear in 49%, and high in 9% of items.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Interest in cell\u2010based injectable therapies for OA treatment is soaring, particularly for alternatives to bone marrow and adipose tissue. While expanded umbilical cord mesenchymal stem cells reported auspicious disease\u2010modifying effects in preventing OA progression in animal models, placenta\/amniotic tissue also reported deleterious effects on OA joints. Lower evidence has been found for other cellular sources such as embryonic, synovial, peripheral blood, dental\u2010pulp, cartilage, meniscus, and muscle\u2010derived products.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>Level II.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ksa.12472","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T08:41:21Z","timestamp":1726821681000},"page":"1695-1708","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cell\u2010based therapies have disease\u2010modifying effects on osteoarthritis in animal models: A systematic review by the ESSKA Orthobiologic Initiative. 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