{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:25:45Z","timestamp":1787307945895,"version":"build-2736575974"},"reference-count":61,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T00:00:00Z","timestamp":1723766400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["HSS Journal\u00ae: The Musculoskeletal Journal of Hospital for Special Surgery"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>Knee osteoarthritis (OA) remains a common cause of knee pain and dysfunction. Stem cell\u2013based injections have been widely used for the treatment of knee OA, but the types and rates of post-injection complications are not well characterized. We sought to characterize the type and severity of adverse events and quantify the frequency of adverse events associated with stem cell injections used to treat knee OA. We conducted a systematic review that followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed and the Cochrane library databases for studies on adverse events and complications associated with stem cell\u2013based therapies used to treat knee OA published from January 2000 through June 2021. Inclusion criteria were the use of intra-articular autologous bone marrow stem cells (BMSCs) or bone marrow aspirate concentrate (BMAC), autologous adipose-derived mesenchymal stem cells (ADMSCs) including microfragmented lipoaspirate, concentrated adipose tissue, cultured stem cells, autologous stromal vascular fraction (SVF), or umbilical or placental derived stem cells in human participants. Primary data extracted from included studies were patient demographics, methods of treatment, and reported character, duration, and severity of adverse events. A total of 427 studies were screened, and 48 studies were included, including randomized controlled trials, prospective studies, and retrospective studies. Among the 1924 patients in the analysis, there was an overall 12.3% rate of transient adverse events, the most frequent being swelling and pain at the injection site. Umbilical cord\u2013derived (51.7%) and cultured ADMSC (29.5%) injections had a significantly higher occurrence of these adverse events than BMSC and SVF injections. No other adverse events, including infection, fat embolism, or medical complications, were reported. Despite significant heterogeneity of the included studies in terms of the protocol, formulation, timing, and location of injections, the findings of this systematic review suggest that, in the short term, treatment of knee OA with autologous mesenchymal stem cell injections poses no risk of major complications (infection, sepsis, neoplasm, embolism, or death) and poses moderate risk of swelling and pain at the injection site lasting less than 4 weeks. Further long-term studies are needed to conclusively determine the safety profile of these injections.<\/jats:p>","DOI":"10.1177\/15563316241271058","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T02:23:06Z","timestamp":1723861386000},"page":"476-484","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Complications of Stem Cell\u2013Based Injections for Knee Osteoarthritis: A Systematic Review"],"prefix":"10.1177","volume":"21","author":[{"given":"Clara","family":"Riggle","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-8284","authenticated-orcid":false,"given":"Maddison","family":"McLellan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunter","family":"Bohlen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, University of California, Irvine, Orange, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,8,16]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"Al-Najar M Khalil H Al-Ajlouni J et al. Intra-articular injection of expanded autologous bone marrow mesenchymal cells in moderate and severe knee osteoarthritis is safe: a phase I\/II study. J Orthop Surg Res. 2017;12(1):1\u20136. https:\/\/doi.org\/10.1186\/s13018-017-0689-6.","DOI":"10.1186\/s13018-017-0689-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","unstructured":"Anz AW Hubbard R Rendos NK Everts PA Andrews JR Hackel JG. Bone marrow aspirate concentrate is equivalent to platelet-rich plasma for the treatment of knee osteoarthritis at 1 year: a prospective randomized trial. Orthop J Sports Med. 2020;8(2):1\u20139. https:\/\/doi.org\/10.1177\/2325967119900958.","DOI":"10.1177\/2325967119900958"},{"issue":"10","key":"e_1_3_2_4_2","first-page":"1","article-title":"Treatment of osteoarthritis with autologous and microfragmented adipose tissue","volume":"66","author":"Barfod KW","year":"2019","unstructured":"Barfod KW, Bl\u00f8nd L. Treatment of osteoarthritis with autologous and microfragmented adipose tissue. 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Stromal vascular fraction cell therapy for osteoarthritis in elderly: multicenter case-control study. J Clin Orthop Trauma. 2019;10(1):76\u201380. https:\/\/doi.org\/10.1016\/j.jcot.2018.11.010.","DOI":"10.1016\/j.jcot.2018.11.010"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","unstructured":"Mora JC Przkora R Cruz-Almeida Y. Knee osteoarthritis: pathophysiology and current treatment modalities. J Pain Res. 2018;11:2189\u20132196. https:\/\/doi.org\/10.2147\/JPR.S154002.","DOI":"10.2147\/JPR.S154002"},{"key":"e_1_3_2_40_2","doi-asserted-by":"crossref","unstructured":"Ong KL Runa M Xiao Z Ngai W Lau E Altman RD. Severe acute localized reactions following intra-articular hyaluronic acid injections in knee osteoarthritis. Cartilage. 2021;13(suppl 1):1474S\u20131486S. https:\/\/doi.org\/10.1177\/1947603520905113.","DOI":"10.1177\/1947603520905113"},{"key":"e_1_3_2_41_2","doi-asserted-by":"crossref","unstructured":"Orozco L Munar A Soler R et al. 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