{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:49:27Z","timestamp":1792622967930,"version":"4.5.0"},"reference-count":33,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T00:00:00Z","timestamp":1756598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N34A650716"],"award-info":[{"award-number":["N34A650716"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Early-stage knee osteoarthritis (knee OA) lacks effective regenerative therapies. This study aimed to compare the cartilage regenerative effects, clinical efficacy, and safety of intra-articular injections of autologous adipose-derived mesenchymal stem cells (ADSCs) versus hyaluronic acid (HA). Forty-eight patients with early knee OA were enrolled in a prospective open-blinded multi-center study at Suranaree University of Technology Hospital and Phramongkutklao Hospital. Participants were randomized into either the ADSC or HA group. Primary outcomes included MRI-based cartilage lesion volume, synovial thickness via ultrasound, and WOMAC scores over 6 months. MRI results revealed significant and progressive cartilage regeneration in the ADSC group. In particular, medial femoral cartilage lesion volume decreased by 50.06 mm3, whereas the HA group showed an increase of 36.44 mm3. Synovial thickness also declined significantly in the ADSC group at 3 and 6 months. Both groups demonstrated reduced symptoms, but the ADSC group achieved superior and sustained improvements in WOMAC pain, stiffness, and function scores throughout the 6-month follow-up. The clinical benefits were consistent and more pronounced compared with HA. No serious adverse events occurred. In conclusion, intra-articular ADSC injections show superior cartilage restoration on MRI and better clinical outcomes than HA injection, making them a promising treatment for early-stage knee OA.<\/jats:p>","DOI":"10.3390\/ijms26178476","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cartilage Regeneration Potential in Early Osteoarthritis of the Knee: A Prospective, Randomized, Open, and Blinded Endpoint Study Comparing Adipose-Derived Mesenchymal Stem Cell (ADSC) Therapy Versus Hyaluronic Acid"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3645-7093","authenticated-orcid":false,"given":"Ponthep","family":"Tangkanjanavelukul","sequence":"first","affiliation":[{"name":"Department of Orthopedics, School of Medicine, Institute of Medicine, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima 30000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saradej","family":"Khuangsirikul","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic, Phramongkutklao College of Medicine, 317 Ratchawithi Road, Thung Phaya Thai, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danai","family":"Heebthamai","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic, Phramongkutklao College of Medicine, 317 Ratchawithi Road, Thung Phaya Thai, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2674-2419","authenticated-orcid":false,"given":"Montarop","family":"Yamabhai","sequence":"additional","affiliation":[{"name":"Molecular Biotechnology Laboratory, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima 30000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thitima","family":"Sumphanapai","sequence":"additional","affiliation":[{"name":"Division of Clinical Hematology and Microscopy, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattapat","family":"Khumtong","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, School of Medicine, Institute of Medicine, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima 30000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanainit","family":"Chotanaphuti","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic, Phramongkutklao College of Medicine, 317 Ratchawithi Road, Thung Phaya Thai, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cger.2010.03.001","article-title":"Epidemiology of osteoarthritis","volume":"26","author":"Zhang","year":"2010","journal-title":"Clin. Geriatr. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.joca.2018.12.018","article-title":"Nature vs. nurture in knee osteoarthritis\u2014The importance of age, sex and body mass index","volume":"27","author":"Magnusson","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100587","DOI":"10.1016\/j.eclinm.2020.100587","article-title":"Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies","volume":"29\u201330","author":"Cui","year":"2020","journal-title":"eClinicalMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ha, C.-W., Park, Y.-B., Choi, C.-H., Kyung, H.-S., Lee, J.-H., Yoo, J.D., Yoo, J.-H., Choi, C.-H., Kim, C.-W., and Kim, H.-C. (2017). Efficacy and safety of single injection of cross-linked sodium hyaluronate vs. three injections of high molecular weight sodium hyaluronate for osteoarthritis of the knee: A double-blind, randomized, multi-center, non-inferiority study. BMC Musculoskelet. Disord., 18.","DOI":"10.1186\/s12891-017-1591-4"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1016\/j.joca.2019.06.011","article-title":"OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis","volume":"27","author":"Bannuru","year":"2019","journal-title":"Osteoarthr. Cartil."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.joca.2010.09.014","article-title":"Therapeutic trajectory following intra-articular hyaluronic acid injection in knee osteoarthritis--meta-analysis","volume":"19","author":"Bannuru","year":"2011","journal-title":"Osteoarthr. Cartil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"180","DOI":"10.7326\/0003-4819-157-3-201208070-00473","article-title":"Viscosupplementation for osteoarthritis of the knee: A systematic review and meta-analysis","volume":"157","author":"Rutjes","year":"2012","journal-title":"Ann. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e23343","DOI":"10.1097\/MD.0000000000023343","article-title":"Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis: A systematic review and meta-analysis","volume":"99","author":"Ma","year":"2020","journal-title":"Medicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1097\/TP.0b013e318291a2da","article-title":"Treatment of knee osteoarthritis with autologous mesenchymal stem cells: A pilot study","volume":"95","author":"Orozco","year":"2013","journal-title":"Transplantation"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s12967-018-1591-7","article-title":"Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: Long-term follow up of a multicenter randomized controlled clinical trial (phase I\/II)","volume":"16","author":"Mora","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/iwj.12569","article-title":"The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery","volume":"14","author":"Naderi","year":"2017","journal-title":"Int. Wound J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2217\/rme-2018-0161","article-title":"Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: A randomized controlled trial","volume":"14","author":"Freitag","year":"2019","journal-title":"Regen. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s13287-019-1248-3","article-title":"Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: A prospective, randomized, double-blind, active-controlled, phase IIb clinical trial","volume":"10","author":"Lu","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"847","DOI":"10.5966\/sctm.2015-0245","article-title":"Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial","volume":"5","author":"Pers","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_15","first-page":"1238","article-title":"Anti-Inflammatory Effect of Cross-Linked Hyaluronic Acids in Osteoarthritic Knee, Detected by Ultrasonography","volume":"7","author":"Khuangsirikul","year":"2020","journal-title":"J. Orthop. Res. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4103\/JMU.JMU_45_20","article-title":"Ultrasonographic Evaluation of Osteoarthritis-affected Knee Joints: Comparison with Kellgren-Lawrence Grading and Pain Scores","volume":"29","author":"Singh","year":"2021","journal-title":"J. Med. Ultrasound"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s42836-020-0024-2","article-title":"Can urinary CTX-II be a biomarker for knee osteoarthritis?","volume":"2","author":"Arunrukthavon","year":"2020","journal-title":"Arthroplasty"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1186\/s13075-016-1195-7","article-title":"Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel\u00ae): Preclinical and clinical trial in osteoarthritis of the knee joint","volume":"18","author":"Gupta","year":"2016","journal-title":"Arthritis Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1002\/stem.1634","article-title":"Intra-Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: A Proof-of-Concept Clinical Trial","volume":"32","author":"Jo","year":"2014","journal-title":"Stem Cells"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s12967-016-0998-2","article-title":"Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: Multicenter randomized controlled clinical trial (phase I\/II)","volume":"14","author":"Mora","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1097\/TP.0000000000000678","article-title":"Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells: A Randomized Controlled Trial","volume":"99","author":"Vega","year":"2015","journal-title":"Transplantation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s13287-019-1406-7","article-title":"Multi-compositional MRI evaluation of repair cartilage in knee osteoarthritis with treatment of allogeneic human adipose-derived mesenchymal progenitor cells","volume":"10","author":"Zhao","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ren, B., Chang, Y., Liu, R., Xiao, F., Xu, J., Li, L., Li, T., Ruan, Z., Bao, Y., and Lin, J. (2023). Clinical phase I\/II trial of SVF therapy for cartilage regeneration: A cellular therapy with novel 3D MRI imaging for evaluating chondral defect of knee osteoarthritis. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1106279"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1177\/0363546519864359","article-title":"Comparative Clinical Outcomes After Intra-articular Injection With Adipose-Derived Cultured Stem Cells or Noncultured Stromal Vascular Fraction for the Treatment of Knee Osteoarthritis","volume":"47","author":"Yokota","year":"2019","journal-title":"Am. J. Sports Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S459","DOI":"10.1016\/j.joca.2020.02.717","article-title":"Effect of highly cross-linked hyaluronic acid in synovitis of knee osteoarthritis","volume":"28","author":"Yuwapan","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1007\/s00167-013-2807-2","article-title":"Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis","volume":"23","author":"Koh","year":"2015","journal-title":"Knee Surg. Sports Traumatol. Arthrosc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s00402-020-03703-0","article-title":"Efficacy and safety of mesenchymal stem cell injections for patients with osteoarthritis: A meta-analysis and review of RCTs","volume":"141","author":"Jiang","year":"2021","journal-title":"Arch. Orthop. Trauma. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1146\/annurev.pathmechdis.3.121806.151456","article-title":"The inflammatory response to cell death","volume":"3","author":"Rock","year":"2008","journal-title":"Annu. Rev. Pathol."},{"key":"ref_29","unstructured":"Chow, S., Shao, J., Wang, H., and Lokhnygina, Y. (2008). Sample size calculations in clinical research, Chapman & Hall."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/RUQ.0000000000000288","article-title":"In-Plane Ultrasound-Guided Knee Injection Through a Lateral Suprapatellar Approach: A Safe Technique","volume":"33","author":"Taneja","year":"2017","journal-title":"Ultrasound Q."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33","DOI":"10.55374\/jseamed.v4i1.55","article-title":"Synovial hypertrophy detected using ultrasonogram in primary osteoarthritic knees: Prevalence and correlation with radiographic staging","volume":"4","author":"Chawanvuth","year":"2020","journal-title":"J. Southeast Asian Med. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"111457","DOI":"10.1016\/j.jclinepi.2024.111457","article-title":"Intention to treat and per protocol analyses: Differences and similarities","volume":"173","author":"Castells","year":"2024","journal-title":"J. Clin. Epidemiol."},{"key":"ref_33","unstructured":"(2023). StataCorp: Stata Statistical Software, Release 18, StataCorp LLC."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8476\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:36:38Z","timestamp":1760034998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,31]]},"references-count":33,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178476"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178476","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,31]]}}}