Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Background: Intra-articular injection of autologous culture-expanded adipose-derived mesenchymal stem cells (ADMSCs) has introduced a promising treatment option for knee osteoarthritis. Although the clinical efficacy and safety of ADMSCs have been reported, the treatment remains controversial owing to the small sample sizes and heterogeneous osteoarthritis grades in previous studies. Purpose: To assess the efficacy and safety of intra-articular injection of ADMSCs as compared with placebo in alleviating pain and improving functional capacity in a large sample of patients with knee osteoarthritis of Kellgren-Lawrence (K-L) grade 3. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: This phase III multicenter clinical trial was a double-blind randomized controlled study that included 261 patients with K-L grade 3 symptomatic knee osteoarthritis who were administered a single injection of autologous culture-expanded ADMSCs or placebo. Clinical data were assessed at baseline and at 3 and 6 months after the injection. The primary endpoints were improvements in 100-mm visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for function at 6 months after the injection. The secondary endpoints included clinical and radiologic examinations and safety after injection. The changes in cartilage defects after injection were assessed by magnetic resonance imaging at 6 months. Results: The ADMSC and control groups included 125 and 127 patients available for follow-up, respectively. At 6 months, the ADMSC group showed significantly better improvements in 100-mm VAS (ADMSC vs control, 25.2 vs 15.5; P = .004) and total WOMAC score (21.7 vs 14.3; P = .002) as compared with the control group. The linear mixed model analysis indicated significantly better improvements in all clinical outcomes in the ADMSC group after 6 months. At 6 months, the ADMSC group achieved significantly higher proportions of patients above the minimal clinically important difference in 100-mm VAS and WOMAC score. Radiologic outcomes and adverse events did not demonstrate significant differences between the groups. No serious treatment-related adverse events were observed. Magnetic resonance imaging revealed no significant difference in change of cartilage defects between the groups at 6 months. Conclusion: Intra-articular injection of autologous culture-expanded ADMSCs provided significant pain relief and functional improvements in patients with K-L grade 3 osteoarthritis. Long-term results are needed to determine the disease-modifying effects of ADMSCs, such as structural changes, and the duration of effect of intra-articular injection of ADMSCs in knee osteoarthritis. Registration: NCT03990805 (ClinicalTrials.gov identifier).

Research on stem cell therapy for spinal cord injury: a bibliometric and visual analysis from 2018–2023

“…The histocompatibility of the tissue engineering scaffolds allows them to address defects in the formation of the cavities and scar tissues and promote the regeneration of axons by improving the microenvironment, and they have also achieved better efficacy in experiments ( Massoto et al, 2020 ). The combination of stem cells, tissue-engineered scaffolds, and neurotrophic factors in cotransplantation and the optimal transplantation method and timing have been studied ( Liu et al, 2019 ; Mafikandi et al, 2019 ; Kim et al, 2023 ). To increase the likelihood of successful tissue engineering, it is important to consider the regenerative environment in the patient’s body, as well as factors such as stiffness, electrical conductivity, and drug release from biomaterials.…”

Transplantation of three mesenchymal stem cells for knee osteoarthritis, which cell and type are more beneficial? a systematic review and network meta-analysis

“…Studies suggest that BM-MSC yield, particularly in the elderly, is relatively low compared to AD-MSC, despite the challenges associated with AD-MSC preparation compared to BM-MSC [ 41 ]. Notably, adipose tissue yields an MSC volume approximately 500 times greater than bone marrow [ 42 , 43 ]. While some researchers assert that BM-MSC exhibits superior cartilage generation capabilities compared to AD-MSC, others propose that augmenting the stromal vascular fraction derived from AD-MSC with growth factors and cytokines can also enhance cartilage growth [ 44 , 45 ].…”

The Role of Extracellular Vesicles in the Pathogenesis and Treatment of Rheumatoid Arthritis and Osteoarthritis

“…The use of MSCs was associated with significantly improved Western Ontario and McMaster Universities Osteoarthritis index score after 6 months of treatment [143]. Recently, positive effects of MSCs have been observed in a phase III trial [144].…”