Safety and Efficacy of Intra-articular Cell-Free Fat Extract Injection in Patients With Symptomatic Knee Osteoarthritis.

[BACKGROUND] Cell-free fat extract (CEFFE) has shown promising therapeutic effects on osteoarthritis (OA) in preclinical studies, but its clinical role remains unclear.

[PURPOSE] To evaluate the safety and efficacy of intra-articular autologous CEFFE injections for symptomatic early- and mid-stage knee OA.

[STUDY DESIGN] Randomized controlled trial; Level of evidence, 2.

[METHODS] A total of 24 participants were randomly allocated to 1 of 4 groups to receive 5 weekly injections of (1) hyaluronic acid (HA, active comparator), (2) low-dose CEFFE (containing 1 mL CEFFE), (3) medium-dose CEFFE (containing 1.5 mL CEFFE), or (4) high-dose CEFFE (containing 2 mL CEFFE). Autologous CEFFE was prepared by spin, emulsification, and filtration after abdominal liposuction, effectively removing lipid and cellular components. Information regarding adverse effects was collected. Routine blood tests, C-reactive protein levels, liver function tests, and kidney function tests were performed at baseline and at the 24-week follow-up to assess systemic toxic effects of CEFFE injection. The clinical effectiveness of CEFFE injections was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores. Magnetic resonance imaging (MRI) was used to detect changes in bone marrow lesions (BMLs) and cartilage loss at baseline and at the final follow-up.

[RESULTS] All patients received the corresponding injections and were followed up for 24 weeks without serious adverse events or clinically significant laboratory abnormalities. At the final follow-up, the mean WOMAC pain subscale score was 5 ± 1.3 in the HA group, compared with 1.5 ± 1.5, 1.7 ± 1, and 1.8 ± 1.7 in the low-, medium-, and high-dose CEFFE groups, respectively. All 3 CEFFE doses were more effective than an intra-articular HA injection for pain relief and recovery of knee function, as assessed by WOMAC and VAS scores. Semi-quantitative MRI analysis indicated greater improvements in BML in CEFFE-treated participants (57.1%) than in controls (16.7%). None of the research groups exhibited a significant improvement in cartilage loss compared with baseline.

[CONCLUSION] CEFFE is an alternative biosafety method for the biological treatment of knee OA, with symptom improvement and BML reduction, and has promising potential for clinical application.