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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 in vivo, 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 ?g ml-1 but showed non-cytotoxic effects at concentrations below 18.8 ?g ml-1. Apoptosis was observed in the TDSCs when higher doses of AgNPs (75-150 ?g ml-1) were used. Mechanistically, AgNPs induced reactive oxygen species (ROS) formation and mitochondrial membrane potential (MMP) depolarization, resulting in apoptosis. Interestingly, treating TDSCs with N-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 ?g ml-1), proliferation and clonogenicity (0-15 ?g ml-1) 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.

SUBMITTER: Cheung TS

PROVIDER: S-EPMC6060715 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Cheung Tik Shing TS Lau Pui Man PM Lu Haifei H Ho Ho Pui HP Lui Pauline Po Yee PPY Kong Siu Kai SK

Toxicology research 20151123 1

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 <i>in vivo</i>, 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 cytotoxicit ...[more]

PMID: 30090348

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Project description:This study aimed to compare clonogenicity, proliferation, stem cell-related marker expression, senescence, and differentiation potential of rat patellar tendon-derived stem cells (TDSCs) at early (P5), mid (P10), and late (P20, P30) passages. The clonogenicity of the cells was assessed by colony-forming assay and their proliferative potential was assessed by bromodeoxyuridine assay. The surface expression of CD90 and CD73 was assessed by flow cytometry. The cellular senescence was assessed by ?-galactosidase activity. The adipogenic, chondrogenic, and osteogenic differentiation potentials of TDSCs were assessed by standard assays after induction. The mRNA expression of tendon-related markers, scleraxis (Scx) and tenomodulin (Tnmd), was measured by quantitative real-time reverse transcription-polymerase chain reaction. Both the colony numbers and proliferative potential of TDSCs increased with passaging. Concomitantly, there was significant upregulation of ?-galactosidase activity with TDSC passaging. The subculture of TDSCs downregulated the expression of CD90 and CD73. Lipid droplets were formed in the early and mid passages of TDSCs upon adipogenic induction, but were absent in the late passages. The expression of peroxisome proliferator activator receptor gamma 2 (PPAR?2) and CCAAT/enhancer binding protein alpha (C/EBP?) in TDSCs after adipogenic induction decreased with passaging. Chondrogenesis, proteoglycan deposition, collagen type II protein expression, collagen type 2A1 (Col2AI), and aggrecan (Acan) mRNA expression were less in pellets formed with later passages of TDSCs after chondrogenic induction. The expression of Scx and Tnmd was lower in the late, compared with early and mid, passages of TDSCs. However, matrix mineralization and expression of alkaline phosphatase (Alpl) and osteocalcin (Bglap) mRNA after osteogenic induction increased with TDSC passaging. Researchers and clinicians should consider the changes of stem cell-related properties of TDSCs when multiplying them in vitro for tissue engineering.

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

Publications

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

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