Cytotoxic and sublethal effects of silver nanoparticles on tendon-derived stem cells – implications for tendon engineering

Abstract

Tendon injuries occur commonly in sports and workplace. Tendon-derived stem cells (TDSCs) have great potential for tendon healing because they can differentiate into functional tenocytes. To grow TDSCs properly , a scaffold is needed. Silver nanoparticles (AgNPs) have been used in a range of biomedical applications for their anti-bacterial and -inflammatory effects. AgNPs are therefore expected to be a good scaffolding coating material for tendon engineering. Yet, their cytotoxicity in TDSCs remains unknown. Moreover, their sublethal effects were mysterious in TDSCs. In our study, decahedral AgNPs (43.5 nm in diameter) coated with polyvinylpyrrolidone (PVP) caused a decrease in TDSCs' viability beginning at 37.5 μg ml but showed non-cytotoxic effects at concentrations below 18.8 μg ml. Apoptosis was observed in the TDSCs when higher doses of AgNPs (75-150 μg ml) were used. Mechanistically, AgNPs induced reactive oxygen species (ROS) formation and mitochondrial membrane potential (MMP) depolarization, resulting in apoptosis. Interestingly, treating TDSCs with -acetyl-l-cysteine (NAC) antioxidant significantly antagonized the ROS formation, MMP depolarization and apoptosis indicating that ROS accumulation was a prominent mediator in the AgNP-induced cytotoxicity. On the other hand, AgNPs inhibited the tendon markers' mRNA expression (0-15 μg ml), proliferation and clonogenicity (0-15 μg ml) in TDSCs under non-cytotoxic concentrations. Taken together, we have reported here for the first time that the decahedral AgNPs are cytotoxic to rat TDSCs and their sublethal effects are also detrimental to stem cells' proliferation and tenogenic differentiation. Therefore, AgNPs are not a good scaffolding coating material for tendon engineering.

Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles

“…In addition, the related studies evaluated the potential impact in terms of acute exposure, i.e. , the short-term exposures to high doses of Ag NPs [ 10 , 11 , 12 ]. However, the real exposure scenario is the long-term exposure to the low-dose of Ag NPs, which may result in different biological sequences compared to the acute exposure to the high-dose of Ag NPs [ 13 , 14 , 15 , 16 ].…”

Roles of Oxidative Stress in Acute Tendon Injury and Degenerative Tendinopathy—A Target for Intervention

“…Treatment of human tenocytes with H 2 O 2 induced apoptosis with cytochrome c release from mitochondria and caspase-3 activation [ 24 ]. N-acetylcysteine (NAC), a cysteine donor and glutathione precursor, was shown to protect rotator cuff fibroblasts from ROS-mediated hypoxic cell apoptosis [ 25 ] and silver nanoparticle-triggered ROS-induced apoptosis of TDSCs [ 26 ]. In addition to cell apoptosis, H 2 O 2 also induced the mRNA expression of matrix metalloproteinase-1 (MMP1) and protein expression of pro-MMP1 in human tendon cells, suggesting that oxidative stress plays an important role in tendon matrix degradation [ 27 ].…”