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  2. Silver nanoparticles (AgNPs) and AgNO3 perturb the specification of human hepatocyte-like cells and cardiomyocytes

Silver nanoparticles (AgNPs) and AgNO3 perturb the specification of human hepatocyte-like cells and cardiomyocytes

  • Sci Total Environ. 2020 Jul 10;725:138433. doi: 10.1016/j.scitotenv.2020.138433.
Bowen Hu 1 Nuoya Yin 2 Renjun Yang 1 Shengxian Liang 1 Shaojun Liang 1 Francesco Faiola 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: nyyin@rcees.ac.cn.
  • 3 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: faiola@rcees.ac.cn.
Abstract

Silver nanoparticles (AgNPs) are commonly utilized industrial compounds mostly because of their antimicrobial properties. Nevertheless, our understanding of their potential developmental toxicity in humans is still limited. Embryonic stem cells (ESCs) are powerful in vitro tools for developmental toxicity assessments of chemicals. Here, we evaluated the potential developmental toxicity during early embryogenesis of AgNPs and AgNO3 with human ESC (hESC)-based differentiation systems in vitro. We found that human relevant concentrations of AgNPs and Ag ions affected the specification of two of the three primary germ layers, endoderm and mesoderm, without drastically affecting ectoderm. Furthermore, the two forms of Ag impaired the generation and functions of hepatocytes-like cells derived from endoderm, by decreasing the expression of important liver markers such as AFP, ALB, and HNF4A, and altering glycogen storage. When considering cardiac development, AgNPs and AgNO3 manifested opposite adverse effects, in that AgNPs increased while AgNO3 decreased the expression of typical cardiac markers (NKX2.5, MYH6, and ISL) in hESC-derived cardiomyocytes. In conclusion, our findings argue for a potential developmental toxicity of AgNP doses we are exposed to, or levels detected in the human body, especially at very early stages during embryogenesis, and which may not be just due to Ag leakage. Moreover, mesendoderm-derived cell types, tissues and organs may be more prone to AgNP toxicity than ectoderm lineages.

Keywords

Cardiomyocytes; Developmental toxicity; Hepatocyte-like cells; Human embryonic stem cells (hESCs); Silver nanoparticles (AgNPs); Stem cell toxicology.

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