Intra-articular adipose-derived cell therapies for knee osteoarthritis: a systematic review of randomized controlled trials

Introduction: Knee osteoarthritis is a leading cause of chronic pain, functional limitation, and disability worldwide, imposing a substantial socioeconomic burden. Despite advances in conservative management and intra-articular therapies, many patients experience limited or transient symptomatic relief, underscoring the need for biologically based interventions. Intra-articular adipose-derived cell therapies, including adipose-derived mesenchymal stem or stromal cells (ADSCs), stromal vascular fraction (SVF), and microfragmented adipose tissue (MFAT), have emerged as regenerative strategies aimed at modulating inflammation and joint homeostasis. This systematic review evaluated the efficacy, structural effects, and safety of intra-articular adipose-derived cell-based therapies for knee osteoarthritis in adults. Methods: Randomized controlled trials published between 2015 and 2025 were identified through systematic searches of PubMed, Embase, Scopus, and Web of Science. Eligible studies compared ADSCs, SVF, or MFAT with placebo, hyaluronic acid, platelet-rich plasma, corticosteroids, or conservative care, and reported outcomes on pain, function, imaging-based structural changes, and safety. Results: Nineteen randomized controlled trials met inclusion criteria. Across studies, adipose-derived interventions, particularly ADSC-based therapies, produced clinically meaningful reductions in pain and improvements in functional outcomes assessed by WOMAC, KOOS, and visual analog scales. Discussion: Several ADSC and SVF trials reported favorable magnetic resonance imaging findings, including improvements in cartilage quality, although consistent cartilage regeneration was not demonstrated. MFAT trials yielded heterogeneous results, often showing symptomatic benefits comparable to established injective therapies but limited structural effects. No serious treatment-related adverse events were reported. Intra-articular adipose-derived cell therapies are safe and provide meaningful pain relief and functional improvement in selected patients, with ADSCs showing the most consistent clinical signals. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251241498, Identifier: CRD420251241498.