Objective: Oxidative stress is a major obstacle against cartilage repair in osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this issue. We evaluated the effect of Vitamin E preconditioning in improving the potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative stress prevailing during OA.
Methods: Vitamin E pretreated MSCs were exposed to oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in surgically-induced rat model of OA. Analysis was done in terms of cell proliferation, apoptosis, cytotoxicity, chondrogenesis and repair of cartilage tissue.
Results: Vitamin E pretreatment enabled MSCs to counteract H2O2-induced oxidative stress in vitro. Proliferative markers, proliferating cell nuclear antigen (PCNA) and Ki67 were up-regulated, along with the increase in the viability of MSCs. Expression of transforming growth factor-beta (TGFβ) was also increased. Reduction of apoptosis, expression of vascular endothelial growth factor (VEGF) and caspase 3 (Casp3) genes, and lactate dehydrogenase (LDH) release were also observed. Transplantation of Vitamin E pretreated MSCs resulted in increased proteoglycan contents of cartilage matrix. Increased expression of chondrogenic markers, Aggrecan (Acan) and collagen type-II alpha (Col2a1) accompanied by decreased expression of collagen type-I alpha (Col1a1) resulted in increased differentiation index that signifies the formation of hyaline cartilage. Further, there was an increased expression of PCNA and TGFβ genes along with a decreased expression of Casp3 and VEGF genes with increased histological score.
Conclusion: Taken together results of this study demonstrated that Vitamin E pretreated MSCs have an improved ability to impede the progression of OA and thus increased potential to treat OA.
Keywords: Antioxidant; Mesenchymal stem cells; Osteoarthritis; Oxidative stress; Vitamin E.
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