Comparison of the therapeutic effect of BMSCs and culture supernatant injection therapy on osteoarthritis and mechanism exploration
Authors: Peng Yiqi , Zhao Rui , Huang Sheng , Xiong Shilin , Yan Qitao , Jin Anmin , yu zhenghong 
Published: May 2020

Abstract
Background

Osteoarthritis (OA) is a chronic disease that can cause disability. The prevalence of osteoarthritis has increased year by year, become a disease that mainly causes the elderly to suffer. With the increasing understanding of bone marrow mesenchymal stem cell (BMSC) in tissue repair, BMSCs shown good therapeutic effects in OA, it may be due to BMSCs exerted their capacities of differentiation, secretion and immunoregulatory in the joints. As previous describe, BMSCs culture supernatant is proved that rich in multiple cytokines. Therefore, how BMSCs injection therapy exerts its ability to exert therapeutic effects, and whether its therapeutic effect can be replaced by its culture supernatant has become the focus of this article.
Methods

In vitro, we designed a co-culture system to deepen understand this new stem cell therapy. Through two kinds of cells cultured alone, direct and indirect cell contact co-culture to observe changes in cell morphology, quantity and cytoplasmic glycoprotein of these two types of cells and changes of the level of growth factor in the culture supernatant to explore the interaction of these two types of cells; in vivo, we induced an OA model and Injected Saline solution, BMSCs and their culture supernatants respectively for treatment, then we compared the improvement results of OA by evaluating changes in the cartilage layer after different treatments. And determine the changes of some growth factors and inflammatory factors in synovial fluid to analyze the possible mechanisms of multiple treatments.
Result

In the co-culture system, it was found that the direct co-culture of BMSCs and OCs can enhance the proliferation ability of OCs, OCs can retain more cytoplasmic glycoprotein, and BMSCs did not occurred abnormal differentiation during the co-culture. In animal experiments, it was found that the ability of BMSCs injection treatment has obvious therapeutic effect on OA, and the effect is better than its supernatant injection treatment. BMSCs therapy reduced matrix loss in articular cartilage cells, and reduced type I collagen production and fibrosis on articular cartilage, effectively regulating EGF and TGF-β1change and inhibited intra-articular inflammation. Supernatant injection treatment will not significantly delay the progress of OA, and it cannot replace BMSCs for the treatment of OA.
Conclusion

BMSCs therapy is a potential new therapy for OA. The secretion and regulation ability of BMSCs plays an important role in the treatment process. BMSCs are activated by the intra-articular environment of OA, regulating growth factors such as EGF and TGFβ to promote articular cartilage regeneration, and reducing intra-articular inflammation by regulating inflammatory factors and delaying the progression of OA. These effects cannot be replaced by the culture supernatant which is rich in multiple factors, and its regulation function requires the presence of BMSCs. These results provide a relatively comprehensive understanding of BMSCs cell therapy in OA and provide a new explanation for the possible anti-inflammatory effects of BMSCs in the joint.