Intra-articular injection of adipose-derived mesenchymal stem cell line attenuates pain, synovitis and cartilage degeneration in monoiodoacetate-induced osteoarthritis rat model

Abstract

Abstract Background: Recently, mesenchymal stem cell therapy has emerged as an option for osteoarthritis (OA) treatment. Intra-articular injection of adipose-derived stem cells (ADSCs) is growing in popularity in clinical practice as conservative treatment for OA. The adipose-derived mesenchymal stem cell line (ASCL) established in our institute provides allogeneic ADSCs that are more purified than conventional ADSCs. This study evaluated the therapeutic efficacy of intra-articular injection of the ASCL using the low-dose monoiodoacetate-OA (MIA-OA) model in rats. Methods: Expression of cell surface markers for ADSCs and the ASCL was examined by flow cytometry. Low-dose MIA-OA model was created in 8-week-old male immunodeficient rats by intra-articular injection of 0.2 mg of MIA on day 0. After MIA injection, treatment group rats underwent intra-articular injection of the ASCL, and control group rats underwent intra-articular injection of ADSCs or vehicle on day 1. All rats subsequently underwent nociception analysis, gait analysis, immunoserological analysis and histopathological analysis. Results: Flow cytometric analysis suggested that the ASCL consists of a homogeneously stem cell population than ADSCs. Nociception analysis revealed that the ASCL rats had higher pain thresholds than ADSCs control rats. Gait analysis revealed that mean swing duration, swing speed and duty cycle were significantly better in the ASCL rats than in vehicle control rats on day 56. Interleukin-6 (IL-6) levels in synovial fluid were significantly lower in the ASCL rats than in vehicle control rats on days 5 and 56. Histopathological scores for infrapatellar synovitis and cartilage erosion were significantly improved in the ASCL rats than in vehicle control rats on days 5 and 56. Conclusions: Intra-articular injection of the ASCL providing allogeneic ADSCs attenuated pain, synovitis and cartilage degeneration both in the early inflammatory phase and in a later less-inflammatory phase in low-dose MIA-OA model. The ASCL injection did not induce any adverse reactions, potentially representing an effective and safe therapeutic option for OA.