Effect of Mesenchymal Stem Cells-Derived Exosomes on the Articular Cartilage of Induced Osteoarthritic Knee Joint in Adult Male versus Female Albino Rats: A Histological and Immunohistochemical Study

Introduction: Osteoarthritis (OA) is a chronic disease that influences many joints, mostly knee joint. Sex-related differences represent a critical role in pathogenesis and severity. Mesenchymal stem cells (MSCs)-derived exosomes have arisen as a therapeutic approach for many disorders. Aim: To evaluate the potential therapeutic effect of MSCs-derived exosomes on osteoarthritic articular cartilage of knee joint in adult male versus female albino rats. Materials & Methods: Seventy (35 male and 35 female) adult albino rats were divided into three groups; each was equally subdivided into a male and a female subgroup. Group I was the control group. Group II was injected with a single knee intra-articular injection of 1 mg monosodium iodoacetate (MIA) to induce OA. Group III was induced by OA, then got a single intra-articular injection of 200 µg exosomes. Blood and knee joint samples were obtained for biochemical, microscopic, morphometric and statistical studies. Results: Group II revealed manifest microscopic changes, that were more prominent in the female subgroup, including apparent decrease in articular cartilage thickness with erosions, and enormous affection of collagen configuration. A highly significant increase in tumor necrosis factor-α (TNF-α) serum level, Mankin’s grading scale and matrix metalloproteinase-9 (MMP-9) immunoreactivity, along with a highly significant decrease in transforming growth factor-β1 (TGF-β1) serum level, collagen mean area percentage and mean color intensity of combined alcian blue/PAS staining were observed. These changes were evidently ameliorated in group III, both in the male and female subgroups. Conclusion: OA-induced changes in knee articular cartilage were more prominent in female than male albino rats. MSCs-derived exosomes can ameliorate these changes both in male and female rats.