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Nanoparticles (NPs) are considered safe for prolonged internalization in cells. During the latest years, an increasing amount of studies indicates cytotoxic effects of different nanoparticles (NPs). On the subject of genotoxicity, carcinogenicity and stem-cell-related toxicity, conflicting results are reported. Stem cells are an important target in several applications of NPs, f.e. in stem cell tracking systems, regenerative medicine and anti-cancer drugs... New insights in the toxicity of nanoparticles on stem cells not only address these aspects, they also contribute to our knowledge on defense mechanisms of different tissues. It is generally known that the intrinsic cellular repair capacity varies with the degree of cell potency, an important matter in developmental toxicity as well as in species- or tissue-related plasticity. Schmidtea mediterranea is a small invertebrate with an easy accessible population of totipotent stem cells. This makes it possible to study underlying mechanisms of nanoparticle toxicity on stem cells in vivo, and as such link them to physiological parameters. We focus on the toxicity and biocompatibility of silver NPs (AgNPs) and silica NPs (SiNPs) on stem-cell-specific activities. Both AgNPs and SiNPs are extensively used in biomedical applications, s.a. disinfectants, implants, as drug carriers or in bio-imaging. In our in vivo model system, we observed the uptake of AgNPs in stem cells via transmission electron microscopy. Stem cells responded by a proliferation decrease, measured via histon H3 immunostaining. We are currently looking into the underlying cause of this decrease, as the genotoxic character of this element is still under debate. Effects on cell cycle progression and differentiation were investigated by looking into the expression of the smedwi-1 gene and corresponding protein levels, both exclusively present in stem cells and indicative for different phases of the cell cycle. At the phenotypic level, concentration-dependent behavioral effects, including looper movements and curling, were observed. Exposure to a range of SiNPs concentrations showed no clear phenotypic or proliferation effects. This is a promising result for the further use of SiNPs, but extra research on the uptake and the effects of coating, and the influence of external parameters are needed for both NP types to confirm initial results.

Nanoparticles (NPs) are considered safe for prolonged internalization in cells.During the latest years, an increasing amount of studies indicates cytotoxic effects of different nanoparticles (NPs). On the subject of genotoxicity, carcinogenicity and stem-cell-related toxicity, conflicting results are reported. Stem cells are an important target in several applications of NPs, f.e. in stem cell tracking systems, regenerative medicine and anti-cancer drugs... New insights in the toxicity of nanoparticles on stem cells not only address these aspects, they also contribute to our knowledge on defense mechanisms of different tissues. It is generally known that the intrinsic cellular repair capacity varies with the degree of cell potency, an important matter in developmental toxicity as well as in species- or tissue-related plasticity. Schmidtea mediterranea is a small invertebrate with an easy accessible population of totipotent stem cells. This makes it possible to study underlying mechanisms of nanoparticle toxicity on stem cells in vivo, and as such link them to physiological parameters. We focus on the toxicity and biocompatibility of silver NPs (AgNPs) and silica NPs (SiNPs) on stem-cell-specific activities. Both AgNPs and SiNPs are extensively used in biomedical applications, s.a. disinfectants, implants, as drug carriers or in bio-imaging. In our in vivo model system, we observed the uptake of AgNPs in stem cells via transmission electron microscopy. Stem cells responded by a proliferation decrease, measured via histon H3 immunostaining. We are currently looking into the underlying cause of this decrease, as the genotoxic character of this element is still under debate. Effects on cell cycle progression and differentiation were investigated by looking into the expression of the smedwi-1 gene and corresponding protein levels, both exclusively present in stem cells and indicative for different phases of the cell cycle. At the phenotypic level, concentration-dependent behavioral effects, including looper movements and curling, were observed. Exposure to a range of SiNPs concentrations showed no clear phenotypic or proliferation effects. This is a promising result for the further use of SiNPs, but extra research on the uptake and the effects of coating, and the influence of external parameters are needed for both NP types to confirm initial results.

Silver nanoparticles (AgNPs) currently belong to the most commercialized nanomaterials, used in both consumer products and medical applications. Despite its omnipresence, in-depth knowledge on the potential toxicity of nanosilver is still lacking, especially for developing organisms. Research on vertebrates is limited due to ethical concerns, and planarians are an ideal invertebrate model to study the effects of AgNPs on stem cells and developing tissues in vivo, as regeneration mimics development by triggering massive stem cell proliferation. Our results revealed a strong interference of AgNPs with tissue- and neuroregeneration which was related to an altered stem cell cycle. The presence of a PVP-coating significantly influenced toxicity outcomes, leading to elevated DNA-damage and decreased stem cell proliferation. Non-coated AgNPs had an inhibiting effect on stem cell and early progeny numbers. Overall, regenerating tissues were more sensitive to AgNP toxicity, and careful handling and appropriate decision making is needed in AgNP applications for healing and developing tissues. We emphasize on the importance of AgNP characterization, as we showed that changes in physicochemical properties influence toxicity. This study was financially supported by Bijzonder Onderzoeksfonds Hasselt University; Fonds Wetenschappelijk Onderzoek Onderzoek Vlaanderen; Province of Limburg and Vlaamse Instelling voor Technologisch Onderzoek.