Silver nanoparticles promote osteogenic differentiation of human urine-derived stem cells at noncytotoxic concentrations

Qin, Hui; An, Zhiquan; Jiang, Yao; Zhao, Yaochao; Wang, Jiaxing; Liu, Xin; Hui, Bing; Zhang, Xianlong; Wang, Yang

doi:10.2147/ijn.s59753

Cited by 121 publications

(85 citation statements)

References 31 publications

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“…AgNPs have a dual role: at lower concentrations, they can enhance cell survival and differentiation, and at higher concentrations, they can inhibit cell viability in neuronal cells [27]. For instance, AgNPs with an average size of 20 nm and at concentrations up to 2 µg/mL promoted osteogenic differentiation of urine-derived stem cells by inducing actin polymerization and activation of RhoA; whereas AgNO 3 had no such effects [28]. To determine the effect of AgNPs on cell survival of four different subpopulations of OvCSCs, we first examined the dose-dependent effect of AgNPs.…”

Section: Resultsmentioning

confidence: 99%

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

Choi

Park

Han

et al. 2016

IJMS

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The cancer stem cell (CSC) hypothesis postulates that cancer cells are composed of hierarchically-organized subpopulations of cells with distinct phenotypes and tumorigenic capacities. As a result, CSCs have been suggested as a source of disease recurrence. Recently, silver nanoparticles (AgNPs) have been used as antimicrobial, disinfectant, and antitumor agents. However, there is no study reporting the effects of AgNPs on ovarian cancer stem cells (OvCSCs). In this study, we investigated the cytotoxic effects of AgNPs and their mechanism of causing cell death in A2780 (human ovarian cancer cells) and OvCSCs derived from A2780. In order to examine these effects, OvCSCs were isolated and characterized using positive CSC markers including aldehyde dehydrogenase (ALDH) and CD133 by fluorescence-activated cell sorting (FACS). The anticancer properties of the AgNPs were evaluated by assessing cell viability, leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and mitochondrial membrane potential (mt-MP). The inhibitory effect of AgNPs on the growth of ovarian cancer cells and OvCSCs was evaluated using a clonogenic assay. Following 1–2 weeks of incubation with the AgNPs, the numbers of A2780 (bulk cells) and ALDH+/CD133+ colonies were significantly reduced. The expression of apoptotic and anti-apoptotic genes was measured by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Our observations showed that treatment with AgNPs resulted in severe cytotoxicity in both ovarian cancer cells and OvCSCs. In particular, AgNPs showed significant cytotoxic potential in ALDH+/CD133+ subpopulations of cells compared with other subpopulation of cells and also human ovarian cancer cells (bulk cells). These findings suggest that AgNPs can be utilized in the development of novel nanotherapeutic molecules for the treatment of ovarian cancers by specific targeting of the ALDH+/CD133+ subpopulation of cells.

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Section: Resultsmentioning

confidence: 99%

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

Choi

Park

Han

et al. 2016

IJMS

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“…hMSCs exposed to different concentrations of AgNPs exhibited no significant changes in alkaline phosphatase activity, osteocalcin gene expression, osteopontin expression, and mineralization [101]. Similarly, AgNPs had no effect on osteogenic differentiation when human urine-derived stem cells were incubated with non-cytotoxic concentrations [102]. …”

Section: Cellular Effects Of Agnps In Stem Cellsmentioning

confidence: 99%

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

Zhang

Shen

Gurunathan

2016

IJMS

241

137

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Silver nanoparticles (AgNPs) have attracted increased interest and are currently used in various industries including medicine, cosmetics, textiles, electronics, and pharmaceuticals, owing to their unique physical and chemical properties, particularly as antimicrobial and anticancer agents. Recently, several studies have reported both beneficial and toxic effects of AgNPs on various prokaryotic and eukaryotic systems. To develop nanoparticles for mediated therapy, several laboratories have used a variety of cell lines under in vitro conditions to evaluate the properties, mode of action, differential responses, and mechanisms of action of AgNPs. In vitro models are simple, cost-effective, rapid, and can be used to easily assess efficacy and performance. The cytotoxicity, genotoxicity, and biocompatibility of AgNPs depend on many factors such as size, shape, surface charge, surface coating, solubility, concentration, surface functionalization, distribution of particles, mode of entry, mode of action, growth media, exposure time, and cell type. Cellular responses to AgNPs are different in each cell type and depend on the physical and chemical nature of AgNPs. This review evaluates significant contributions to the literature on biological applications of AgNPs. It begins with an introduction to AgNPs, with particular attention to their overall impact on cellular effects. The main objective of this review is to elucidate the reasons for different cell types exhibiting differential responses to nanoparticles even when they possess similar size, shape, and other parameters. Firstly, we discuss the cellular effects of AgNPs on a variety of cell lines; Secondly, we discuss the mechanisms of action of AgNPs in various cellular systems, and try to elucidate how AgNPs interact with different mammalian cell lines and produce significant effects; Finally, we discuss the cellular activation of various signaling molecules in response to AgNPs, and conclude with future perspectives on research into AgNPs.

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“…20 Recent advancements in stem cell research show that stem cells used as seed cells have unique properties that are vital to the development of engineered tissue constructs, including high proliferation rates, self-renewal, and specialized differentiation under specific conditions. 21 In addition, differentiated stem cells are less resistant to chemotherapy than non-differentiated cells. AgNPs act as either differentiation-inducing or cytotoxic agent, depending on their concentration and the cell type.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, AgNPs were shown to promote osteogenic differentiation of urine-derived stem cells by inducing actin polymerization, increasing cytoskeletal tension, and activating RhoA. 21 In contrast, AgNPs were found to inhibit differentiation via autophagy blockade and lysosomal impairment in THP-1 monocytes. 22 Several studies have reported that AgNPs play an important role in tissue engineering scaffolds, with a reduced incidence of infection and significant cell compatibility.…”

Section: Introductionmentioning

confidence: 99%

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy

Han

Gurunathan

Choi

et al. 2017

IJN

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Background Silver nanoparticles (AgNPs) exhibit strong antibacterial and anticancer activity owing to their large surface-to-volume ratios and crystallographic surface structure. Owing to their various applications, understanding the mechanisms of action, biological interactions, potential toxicity, and beneficial effects of AgNPs is important. Here, we investigated the toxicity and differentiation-inducing effects of AgNPs in teratocarcinoma stem cells. Materials and methods AgNPs were synthesized and characterized using various analytical techniques such as UV–visible spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. The cellular responses of AgNPs were analyzed by a series of cellular and biochemical assays. Gene and protein expressions were analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. Results The AgNPs showed typical crystalline structures and spherical shapes (average size =20 nm). High concentration of AgNPs induced cytotoxicity in a dose-dependent manner by increasing lactate dehydrogenase leakage and reactive oxygen species. Furthermore, AgNPs caused mitochondrial dysfunction, DNA fragmentation, increased expression of apoptotic genes, and decreased expression of antiapoptotic genes. Lower concentrations of AgNPs induced neuronal differentiation by increasing the expression of differentiation markers and decreasing the expression of stem cell markers. Cisplatin reduced the viability of F9 cells that underwent AgNPs-induced differentiation. Conclusion The results showed that AgNPs caused differentially regulated cytotoxicity and induced neuronal differentiation of F9 cells in a concentration-dependent manner. Therefore, AgNPs can be used for differentiation therapy, along with chemotherapeutic agents, for improving cancer treatment by targeting specific chemotherapy-resistant cells within a tumor. Furthermore, understanding the molecular mechanisms of apoptosis and differentiation in stem cells could also help in developing new strategies for cancer stem cell (CSC) therapies. The findings of this study could significantly contribute to the nanomedicine because this study is the first of its kind, and our results will lead to new strategies for cancer and CSC therapies.

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Silver nanoparticles promote osteogenic differentiation of human urine-derived stem cells at noncytotoxic concentrations

Cited by 121 publications

References 31 publications

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells

Silver Nanoparticle-Mediated Cellular Responses in Various Cell Lines: An in Vitro Model

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy

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