Assessing the biocompatibility of silver nanoparticles with Schmidtea mediterranea, a stem cell model organism

Because of their antibacterial and anti-inflammatory properties, silver nanoparticles (AgNPs) are among the nanomaterials most often incorporated in nanofunctionalised consumer products such as paints, food containers, clothing and surgical instruments, and are considered beneficial for tissue regeneration and wound repair. Despite their industrial and medical advantages, AgNPs have a cyto- and genotoxic potential and can affect different tissues and cell types, including stem cells, which are a relevant target of nanoparticles. This makes an in-depth knowledge on stem cell toxicology essential in understanding the heterogeneity of toxic responses, especially in developmental and carcinogenic tissues. We assessed the biocompatibility of non-coated (NC) and polyvinylpyrrolidone (PVP) coated spherical AgNPs using the stem cell model organism, Schmidtea mediterranea. This free-living freshwater triclad (planarian) allows uncomplicated set-ups and high-throughput screening and is uniquely positioned because of its easily accessible population of adult somatic stem cells. As such, it is possible to study underlying mechanisms of nanoparticle toxicity on stem cells in vivo, and link them to physiological parameters like regeneration and development. After a physicochemical AgNP characterisation and cellular uptake and localization study, a sensitivity screen revealed a higher susceptibility for regenerating compared to fully developed organisms. An in-depth assessment of molecular, cellular and physiological effects showed a delayed neurodevelopment at all levels, which was stronger for PVP-AgNP. AgNPs also decreased the motility of regenerating S. mediterranea and changed the type of motility behavior in a concentration-dependent way. Underlying to the behavioral effects, a significant inhibition of brain and eye regeneration was observed. This is probably caused by altered stem cell dynamics, as an exposure to different concentrations of AgNPs induced a significant decrease in stem cell proliferation. The reduced stem cell proliferation also induced an overall delay in tissue development resulting in a smaller blastema. The results of this ongoing research project indicate that effects of AgNPs on development processes in S. mediterranea are factual and should be considered in future risk analysis.