Feasibility and safety of GMP-produced stromal vascular fraction for treatment of knee osteoarthritis: a phase I, first-in-human clinical study with two separated injections

The stromal vascular fraction (SVF), derived from adipose tissue, holds promise for the treatment of osteoarthritis (OA) owing to its regenerative and immunomodulatory properties. Clinical implementation, however, is constrained by logistical and regulatory challenges. This first-in-human, phase I clinical study evaluates the feasibility and safety of good manufacturing practice (GMP)–produced, cryopreserved autologous SVF administered in two separate injections in patients with advanced knee OA, and reports exploratory, patient-reported clinical outcomes. Ten patients with Kellgren–Lawrence grade 3–4 OA underwent liposuction yielding 250 mL of adipose tissue, which was processed mechanically at our GMP facility. The resulting SVF was cryopreserved and injected at baseline and three months later into the infrapatellar (Hoffa’s) fat pad. Quality control included viability assessment, sterility testing and flow cytometry. Efficacy was assessed with the Knee injury and Osteoarthritis Outcome Score (KOOS) over a 12-month period. Nine patients completed both injections without serious adverse events. Post-thaw viability was 62.1% for the total SVF and 78.3% for adipose-derived stem cells (ASCs; CD45 - CD31 - CD34 + ). KOOS scores improved by a median of + 13.5 points (IQR 2.7–29.4) at 12 months, with 8 of 9 patients showing improvement (Wilcoxon signed-rank test, p = 0.020). Exploratory correlation between ASC dose and KOOS change was not statistically significant. GMP-based SVF production and repeated intra–fat pad dosing are feasible and safe. Exploratory patient-reported outcomes showed improvement in KOOS at 6 and 12 months, but the small, uncontrolled cohort and heterogeneous dosing preclude any conclusion about efficacy. These findings support further investigation in larger, controlled trials designed and powered to optimise dosing and evaluate treatment effect.