Efficacy and Safety of Intra-Articular Cell-Based Therapy for Osteoarthritis: Systematic Review and Network Meta-Analysis

Abstract

Objective Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of articular cartilage and secondary osteogenesis. Cell-based agents, such as mesenchymal stem cells, have turned into the most extensively explored new therapeutic agents for OA. However, evidence-based research is still lacking. Methods We searched public databases up to February 2020 and only included randomized controlled trials. The outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee Injury and Osteoarthritis Outcome Score (KOOS), the visual analogue scale (VAS) score, and serious adverse events (SAEs). A network meta-analysis was also performed in this work. Results We included 13 studies in the meta-analysis. The effect size showed that cell-based therapy did not significantly reduce the WOMAC score at the 6-month follow-up (standard mean difference [SMD] −3.6; 95% confidence interval [CI] −0.90 to 0.18; P = 0.1928). However, cell-based therapy significantly improved the KOOS at the 12-month follow-up (SMD 0.68; 95% CI 0.07-1.30; P = 0.0288) and relieved pain (SMD −1.05; 95% CI −1.46 to −0.64; P < 0.0001). The findings also indicated that high-dosage adipose-derived mesenchymal stem cells (ADMSCs) may be more advantageous in terms of long-term effects. Conclusions Cell-based therapy had a better effect on KOOS improvement and pain relief without safety concerns. However, cell-based therapy did not show a benefit in terms of the WOMAC. Allogeneic cells might have advantages compared to controls in the WOMAC and KOOS scores. The long-term effect of high-dose ADMSC treatment for OA is worthy of further study.

Intra-articular Injection of Mesenchymal Stem Cells After High Tibial Osteotomy in Osteoarthritic Knee: Two-Year Follow-up of Randomized Control Trial

“… 10 , 20 , 21 In this context, recent meta-analyses with randomized-control trials (RCTs) have shown that intra-articular injection of MSCs led to significant pain relief and functional improvement with safety in patients with knee OA after the injection. 22-24 However, the obvious efficacy of MSCs on articular cartilage regeneration remains still unclear. 22-24 …”

Efficacy and safety of intra-articular therapies in rheumatic and musculoskeletal diseases: an overview of systematic reviews

“…A network meta-analysis analysed the effect of MSC against different comparators, including placebo, HA, or IA GC. 24 The effect of MSC was moderate to large on pain and moderate for the KOOS at 12 months, whereas no effect was observed on the WOMAC total score at 6 months. High-dose adipose-derived MSC showed a longer effect.…”

“…Our strategy only retrieved one SR in KOA that met our inclusion criteria. 24 Moderate to large effects were seen for KOOS and pain, respectively, that lasted until 12 months of follow-up. However, the data in which to draw firm conclusions were scarce.…”

Fat Graft in Surgical Treatment of Medication-Related Osteonecrosis of the Jaws (MRONJ)

“…These extracellular vesicles have been found to release miR-21, miR-181b, matrix metalloproteinases, milk fat globule EGF (MFG-E8), angiopoietin-like 1, and miR-375 to promote the neoangiogenesis during soft tissue healing and induce osteoblast differentiation and bone regeneration [47][48][49]. This expanded knowledge strongly promoted the initial enthusiasm in ASCs-based therapy, and during the following years, several investigations studied their clinical applicability to treat, among the others, osteoarthritis [50], Parkinson's disease [51], stroke [52,53], diabetic kidney disease [54], spinal cord injury [55], cutaneous scars [56], chronic skin wounds and soft tissues defects [57], burn wounds [58], alveolar ridge regeneration [59], Chron's disease [60], liver regeneration after partial hepatectomy [61], Graft-versus-Host disease [62], facial nerve regeneration [63], and intervertebral disc degeneration [64]. Nevertheless, it should be underlined that most of the initial expectations regarding the osteogenic properties of ASCs have been downsized by the following researchers, who demonstrated their limited differentiation potential toward osteogenic lineage [65].…”