Autologous Adipose-Derived Stem Cell Injections for Knee Osteoarthritis

This multicenter, prospective, randomized, active-controlled, single-blind (assessor-blinded) clinical trial aims to evaluate the efficacy and safety of intra-articular injection of autologous adipose-derived mesenchymal stem cells (ADMSCs) compared with active comparator hyaluronic acid (HA) in patients with Kellgren-Lawrence grade II to III knee osteoarthritis. A total of 165 participants across 3 centers (Severance Hospital, Seoul National University Hospital, Inha University Hospital) will be randomly allocated to either the ADMSC group (1.0 x 10\^8 cells, single injection) or the HA group (Synovian, 3 mL) in a 2:1 ratio and followed for 6 months post-injection.

Inclusion Criteria: 1. Adults aged 40 to 70 years at the time of written informed consent. 2. Knee osteoarthritis diagnosed according to American College of Rheumatology (ACR) criteria with persistent knee pain for at least 3 months. 3. Radiographic Kellgren-Lawrence (KL) grade II or grade III in the target knee. 4. Activity pain score of \>= 40 mm on a 100-mm Visual Analog Scale (VAS) in the target knee. 5. Unilateral or bilateral knee OA. In bilateral cases, one target knee must be designated according to criteria 1-4 (if both knees meet criteria, the more painful/symptomatic knee is selected). 6. Voluntary provision of written informed consent. Exclusion Criteria: 1. Secondary knee osteoarthritis caused by infection, rheumatoid arthritis, or inflammatory joint disease. 2. Pain caused by meniscus posterior horn root tear within 3 months prior to screening. 3. Pain judged to be caused by subchondral insufficiency fracture or osteonecrosis. 4. Conditions affecting joint pain or prognosis (e.g., gout, pseudogout, periarticular fracture, hemochromatosis, Wilson's disease, hypermobility, collagen gene disorders). 5. Body Mass Index (BMI) \>= 35 kg/m2. 6. Prior total knee arthroplasty (TKA) or unicompartmental knee arthroplasty (UKA) in the target knee (prior HTO or partial meniscectomy \>= 6 months with stable status is permitted). 7. Recent target knee treatments: cross-linked HA, cell therapy, or gene therapy within 6 months; linear HA or intra-articular corticosteroid within 3 months; oral NSAIDs, glucosamine, chondroitin, or oral steroids within 14 days prior to injection. 8. Uncontrolled type 1 or type 2 diabetes (HbA1c \> 8.5% at screening). 9. Positive test for Human Immunodeficiency Virus (HIV) antibody. 10. History of malignant neoplasm within 3 years prior to screening. 11. Participation in another clinical trial within 60 days prior to screening. 12. Clinically significant abnormal screening laboratory findings. 13. Psychiatric disorder, alcohol/drug abuse affecting adherence or safety. 14. Pregnant or breastfeeding women. 15. Women of childbearing potential or men unwilling to use medically acceptable contraception during the trial. 16. Judged ineligible by the investigator.