Evaluation of the healing effect of kappa-carrageenan combined with dental pulp stem cell-derived exosomes on induced knee osteoarthritis in male rats.

Abstract

Osteoarthritis (OA) is a degenerative joint disease that causes pain and reduces quality of life. Exosomes, dental pulp stem cells, and kappa carrageenan are arising as potential therapies for enhancing cartilage regeneration. The aim of this study is to evaluate the combined therapeutic effects of exosomes, dental pulp stem cells, and kappa carrageenan in reducing osteoarthritis severity. Fifty-four male Sprague Dawley rats (10-wk-old, 200 ± 20 gr) were divided into nine groups. Human dental pulp stem cells (HDPSCs) were isolated from healthy third Molars of human teeth and cultured. Osteoarthritis was induced by anterior cruciate ligament transection. Treatments included intra-articular injections of kappa carrageenan, exosomes, HDPSCs, or their combinations. Ten weeks after treatment, knee joints were obtained and prepared for histopathological evaluation. Radiological evaluations were performed with CBCT imaging. A p-value of less than 0.05 is considered statistically significant. The group treated with Exosomes, Carrageenan, HDPSCs (ECD group) showed the most substantial reduction in Total Radiology and Osteophyte scores (p < 0.0001 and p = 0.0003, respectively). The exosome with HDPSCs group also showed significant improvements (p = 0.0002 and p = 0.0005). Histopathological analysis showed that the ECD group had significantly better cartilage integrity, matrix structure, and cell viability (p = 0.0225, p = 0.0002, and p = 0.0009). In Masson's Trichrome and Safranin O staining, the ECD, ED, and EC-treated groups demonstrated improved matrix quality with better collagen alignment. The intraarticular injection of the combination of exosomes, carrageenan, and HDPSCs significantly improved both the radiological and histopathological results in an osteoarthritis model.