Clinical Efficacy of Intra-articular Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Double-Blinded Prospective Randomized Controlled Clinical Trial

Abstract

Background: Currently, there are limited nonoperative treatment options available for knee osteoarthritis (OA). Cell-based therapies have emerged as promising treatments for knee OA. Autologous stromal vascular fraction (SVF) has been identified as an efficient medium for intra-articular administration of progenitor cells and mesenchymal stem cells derived from adipose tissue. Hypothesis: Patients receiving intra-articular SVF would show significantly greater improvement than patients receiving placebo injections, and this improvement would be dose dependent. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This was a multisite prospective double-blinded randomized placebo-controlled clinical trial. Adult patients with symptomatic knee OA were eligible. Thirty-nine patients were randomized to high-dose SVF, low-dose SVF, or placebo (1:1:1). SVF was obtained via liposuction, processed to create the cellular implant, and injected during the same clinical visit. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and magnetic resonance images were obtained preoperatively and at 6 and 12 months after injection. The Wilcoxon rank sum nonparametric test was utilized to assess statistical significance, and the Hodges-Lehmann location shift was used to assess superiority. Results: The median percentage change in WOMAC score at 6 months after injection for the high-dose, low-dose, and placebo groups was 83.9%, 51.5%, and 25.0%, respectively. The high- and low-dose groups had statistically significant changes in WOMAC scores when compared with the placebo group (high dose, P = .04; low dose, P = .02). The improvements were dose dependent. The median percentage change in WOMAC score from baseline to 1 year after injection for the high-dose, low-dose, and placebo groups was 89.5%, 68.2%, and 0%, respectively. The high- and low-dose groups displayed a greater percentage change at 12 months when compared with the placebo group (high dose, P = .006; low dose, P = .009). Magnetic resonance image review revealed no changes in cartilage thickness after treatment. No serious adverse events were reported. Conclusion: Intra-articular SVF injections can significantly decrease knee OA symptoms and pain for at least 12 months. The efficacy and safety demonstrated in this placebo-controlled trial support its implementation as a treatment option for symptomatic knee OA. Registration: NCT02726945 (ClinicalTrials.gov identifier)

Treatment of Grade 3 and 4 Osteoarthritis with Intraoperatively Separated Adipose Tissue-Derived Stromal Vascular Fraction: A Comparative Case Series

“…It can be considered a successful regeneration of the articular cartilage if a formation of hyaline cartilage can be found on the surface of the joints. Previous studies have shown the de novo formation of hyaline-like cartilage after treatment with ASCs and umbilical cord blood-derived MSCs [24,25]. The second occurrence that could be observed on the MRI images was a widening of the joint space 14 months after the SVF treatment.…”

“…In both treatment groups, an improvement of the clinical parameters was observed. In the case of this study, the effects were dose-dependent, with higher dose showing higher effects [25]. In this case series, we did not administer predefined numbers of SVF cells but the maximum number that could be collected from each patient's tissue, which was on average 7.56 × 10 6 SVF cells.…”

Infrapatellar Fat Pad/Synovium Complex in Early-Stage Knee Osteoarthritis: Potential New Target and Source of Therapeutic Mesenchymal Stem/Stromal Cells

“…MSC-based therapy to treat OA has received attention based on promising pre-clinical reports. Various cell sources have been successfully used in early-phase clinical trials, including bone marrow (Orozco et al, 2014;Vega et al, 2015;Soler et al, 2016), umbilical cord (Matas et al, 2019), and adipose-derived stromal vascular fraction (Garza et al, 2020). A recent systematic review summarizing available studies testing intra-articular MSC therapy for OA and chondral defects concluded that the therapy is safe with clinical and in some cases imaging improvement (McIntyre et al, 2018).…”

Clinical Translational Potential in Skin Wound Regeneration for Adipose-Derived, Blood-Derived, and Cellulose Materials: Cells, Exosomes, and Hydrogels

“…These preclinical “proof of principle” analyses have determined that both freshly isolated and cryopreserved human ASCs can accelerate and enhance the rate of skin wound healing [ 48 ] ( Figure 1 ). Indeed, by performing the isolation procedure on lipoaspirates harvested at the time of a single operation and immediately implanting the recovered cells, regulators have authorized such autologous adipose cell products to advance into clinical trials [ 49 ]; however, to date, none of these devices are used routinely in the United States as a basis for skin wound therapy. Furthermore, while sophisticated adipose-derived cell therapies are feasible as elective procedures in a civilian hospital of an industrialized country, these would not be practical in less advanced environments, such as a poorly resourced hospital in a developing nation or under conditions encountered on the battlefield.…”