Suter-Dick, Laura

Lade...
Profilbild
E-Mail-Adresse
Geburtsdatum
Projekt
Organisationseinheiten
Berufsbeschreibung
Nachname
Suter-Dick
Vorname
Laura
Name
Suter-Dick, Laura

Suchergebnisse

Gerade angezeigt 1 - 10 von 10
  • Publikation
    Environmentally relevant UV-light weathering of polystyrene micro- and nanoplastics promotes hepatotoxicity in a human cell line
    (Royal Society of Chemistry, 2023) Englert, Felix H.; Mueller, Fabrice A.; Dugershaw-Kurzer, Battuja; Kissling, Vera M.; Boentges, Sarah; Gupta, Govind S.; Fontana, Gabriele A.; Diedrich, Sabine; Suter-Dick, Laura; Sturla, Shana J.; Buerki-Thurnherr, Tina [in: Environmental Science: Nano]
    Environmentally-relevant concentrations of UV-weathered polystyrene micro and nanoplastics induce hepatotoxicity and considerable changes in gene expression of liver disease-relevant pathways.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    How to Foster ‘New Approach Methodology’ Toxicologists
    (SAGE, 18.02.2022) Doktorova, Tatyana Y.; Azzi, Pamela; Hofer, Joelle; Werner, Sophie; Singh, Pranika; Hardy, Barry; Chesne, Christophe; Messner, Catherine; Gaiser, Carine; Suter-Dick, Laura [in: Alternatives to Laboratory Animals]
    The need to reduce, refine and replace animal experimentation has led to a boom in the establishment of new approach methodologies (NAMs). This promising trend brings the hope that the replacement of animals by using NAMs will become increasingly accepted by regulators, included in legislation, and consequently more-often implemented by industry. The majority of NAMs, however, are still not very well understood, either due to the complexity of the applied approach or the data analysis workflow. A potential solution to this problem is the provision of better educational resources to scientists new to the area — showcasing the added value of NAMs and outlining various ways of overcoming issues associated with knowledge gaps. In this paper, the educational exchange between four institutions — namely, two universities and two SMEs — via a series of video training sessions, is described. The goal of this exchange was to showcase an exemplary event to help introduce scientists to non-animal approaches, and to actively support the development of resources enabling the use of alternatives to laboratory animals.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Evaluation of dioxin induced transcriptomic responses in a 3D human liver microtissue model
    (Elsevier, 2022) Tian, Mingming; Gou, Xiao; Zhang, Xiaowei; Messner, Catherine; Suter-Dick, Laura; Yan, Lu [in: Environmental Research]
    Three-dimensional human liver microtissue model provides a promising method for predicting the human hepatotoxicity of environmental chemicals. However, the dynamics of transcriptional responses of 3D human liver microtissue model to dioxins exposure remain unclear. Herein, time-series transcriptomic analysis was used to characterize modulation of gene expression over 14 days in 3D human liver microtissues exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD, 31 nM, 10 ng/ml). Changes in gene expression and modulation of biological pathways were evaluated at several time points. The results showed that microtissues stably expressed genes related to toxicological pathways (e.g. highly of genes involved in external stimuli and maintenance of cell homeostasis pathways) during the 14-day culture period. Furthermore, a weekly phenomenon pattern was observed for the number of the differentially expressed genes in microtissues exposed to TCDD at each time point. TCDD led to an induction of genes involved in cell cycle regulation at day three. Metabolic pathways were the main significantly induced pathways during the subsequent days, with the immune/inflammatory response enriched on the fifth day, and the cellular response to DNA damage was identified at the end of the exposure. Finally, relevant transcription patterns identified in microtissues were compared with published data on rodent and human cell-line studies to elucidate potential species-specific responses to TCDD over time. Cell development and cytochrome P450 pathway were mainly affected after a 3-day exposure, with the DNA damage response identified at the end of exposure in the human microtissue system but not in mouse/rat primary hepatocytes models. Overall, the 3D human liver microtissue model is a valuable tool to predict the toxic effects of environmental chemicals with a relatively long exposure.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Assessment of fibrotic pathways induced by environmental chemicals using 3D-human liver microtissue model
    (Elsevier, 30.12.2020) Lu, Yan; Messner, Catherine; Suter-Dick, Laura [in: Environmental Research]
    Exposure to environmental chemicals, particularly those with persistent and bioaccumulative properties have been linked to liver diseases. Induction of fibrotic pathways is considered as a pre-requirement of chemical induced liver fibrosis. Here, we applied 3D in vitro human liver microtissues (MTs) composed of HepaRG, THP-1 and hTERT-HSC that express relevant hepatic pathways (bile acid, sterol, and xenobiotic metabolism) and can recapitulate key events of liver fibrosis (e.g. extracellular matrix-deposition). The liver MTs were exposed to a known profibrotic chemical, thioacetamide (TAA) and three representative environmental chemicals (TCDD, benzo [a] pyrene (BaP) and PCB126). Both TAA and BaP triggered fibrotic pathway related events such as he-patocellular damage (cytotoxicity and decreased albumin release), hepatic stellate cell activation (transcriptional upregulation of α-SMA and Col1α1) and extracellular matrix remodelling. TCDD or PCB126 at measured con-centrations did not elicit these responses in the 3D liver MTs system, though they caused cytotoxicity in HepaRG monoculture at high concentrations. Reduced human transcriptome (RHT) analysis captured molecular re-sponses involved in liver fibrosis when MTs were treated with TAA and BaP. The results suggest that 3D, multicellular, human liver microtissues represent an alternative, human-relevant, in vitro liver model for assessing fibrotic pathways induced by environmental chemicals.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Swiss Startup Framework: A Highly Effective Network Supporting the Generation of Emerging Biotech Businesses
    (Schweizerische Chemische Gesellschaft, 28.10.2020) Suter-Dick, Laura; Mitchell, Isabelle [in: Chimia]
    For over 50 years, Switzerland has been one of the leading countries driving innovation in biotechnology and its industrial applications. Today, some 1,000 biotech companies form a tightly knit, cross-functional network ranging from research through to manufacturing. This network comprises R&D companies, contract research organizations, and highly specialized advisors and biotech investors. Together, they form an external innovation pool that complements the in-house R&D capacity of the large multi-national pharma companies. A highly effective startup framework, solid acceleration mechanisms, and innovative investors enable the emergence of a continuous flow of biotech startups that revitalize the industry with new technologies and products supporting drug development and diagnostics.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Exosomal microRNAs Release as a Sensitive Marker for Drug-Induced Liver Injury In Vitro
    (Mary Ann Liebert, 16.09.2020) Messner, Catherine; Premand, Carine; Gaiser, Carine; Kluser, Tanja; Kübler, Eric; Suter-Dick, Laura [in: Applied In Vitro Toxicology]
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Rat multicellular 3D liver microtissues to explore TGF-β1 induced effects
    (Elsevier, 13.11.2019) Prestigiacomo, Vincenzo; Weston, Anna; Suter-Dick, Laura [in: Journal of Pharmacological and Toxicological Methods]
    Chronic liver damage can lead to fibrosis, encompassing hepatocellular injury, activation of Kupffer cells (KC), and activation of hepatic stellate cells (HSC). Inflammation and TGF-β1 are known mediators in the liver fibrosis adverse outcome pathway (AOP). The aim of this project was to develop a suitable rodent cell culture model for the investigation of key events involved in the development of liver fibrosis, specifically the responses to pathophysiological stimuli such as TGF-β1 and LPS-triggered inflammation. We optimized a single step protocol to purify rat primary hepatocytes (Hep), HSC and KC cells to generate 3D co-cultures based on the hanging drop method. This primary multicellular model responded to the profibrotic cytokine TGF-β1 (1 ng/mL) with signs of hepatocellular damage, inflammation and ultimately HSC activation (increase in αSMA expression). LPS elicited an inflammatory response characterized by increased expression of cytokines. 3D-monocultures comprising only Hep displayed different responses, underlying that parenchymal and non-parenchymal cells need to be present in the system to recapitulate fibrosis. The data also suggest that pre-activated HSC may reverse to a quiescent phenotype in 3D, probably due to the more physiological conditions.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Nrf2 protects stellate cells from Smad-dependent cell activation
    (Public Library of Science, 07/2018) Prestigiacomo, Vincenzo; Suter-Dick, Laura [in: PLOS ONE]
    Hepatic stellate cells (HSC) orchestrate the deposition of extracellular matrix (ECM) and are the primary effector of liver fibrosis. Several factors, including TGF-β1, PDGF and oxidative stress, have been shown to trigger HSC activation. However, the involvement of cellular defence mechanisms, such as the activation of antioxidant response by Nrf2/Keap1 in the modulation of HSC activation is not known. The aim of this work was to elucidate the role of Nrf2 pathway in HSC trans-differentiation involved in the development of fibrosis. To this end, we repressed Nrf2 and Keap1 expression in HSC with specific siRNAs. We then assessed activation markers, as well as proliferation and migration, in both primary and immortalised human HSCs exposed to Smad inhibitors (SB-431542 hydrate and SB-525334), TGF-β1 and/or PDGF. Our results indicate that knocking down Nrf2 induces HSC activation, as shown by an increase in αSMA-positive cells and by gene expression induction of ECM components (collagens and fibronectin). HSC with reduced Nrf2-levels also showed an increase in migration and a decrease in proliferation. We could also demonstrate that the activation of Nrf2-deficient HSC involves the TGF-β1/Smad pathway, as the activation was successfully inhibited with the two tested Smad inhibitors. Moreover, TGF-β1 elicited a stronger induction of HSC activation markers in Nrf2 deficient cells than in wild type cells. Thus, our data suggest that Nrf2 limits HSCs activation, through the inhibition of the TGF-β1/Smad pathway in HSCs.
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Key Challenges and Opportunities Associated with the Use of In Vitro Models to Detect Human DILI: Integrated Risk Assessment and Mitigation Plans
    (Hindawi Publishing Corporation, 09/2016) Suter-Dick, Laura; Atienzar, Franck A; Blomme, Eric A. [in: BioMed Research International]
    01A - Beitrag in wissenschaftlicher Zeitschrift
  • Publikation
    Stem cell-derived systems in toxicology assessment
    (Mary Ann Liebert, 07/2015) Suter-Dick, Laura; Alves, Paula M.; Blaauboer, Bas J. [in: Stem Cells and Development]
    Industrial sectors perform toxicological assessments of their potential products to ensure human safety and to fulfill regulatory requirements. These assessments often involve animal testing, but ethical, cost, and time concerns, together with a ban on it in specific sectors, make appropriate in vitro systems indispensable in toxicology. In this study, we summarize the outcome of an EPAA (European Partnership of Alternatives to Animal Testing)-organized workshop on the use of stem cell-derived (SCD) systems in toxicology, with a focus on industrial applications. SCD systems, in particular, induced pluripotent stem cell-derived, provide physiological cell culture systems of easy access and amenable to a variety of assays. They also present the opportunity to apply the vast repository of existing nonclinical data for the understanding of in vitro to in vivo translation. SCD systems from several toxicologically relevant tissues exist; they generally recapitulate many aspects of physiology and respond to toxicological and pharmacological interventions. However, focused research is necessary to accelerate implementation of SCD systems in an industrial setting and subsequent use of such systems by regulatory authorities. Research is required into the phenotypic characterization of the systems, since methods and protocols for generating terminally differentiated SCD cells are still lacking. Organotypical 3D culture systems in bioreactors and microscale tissue engineering technologies should be fostered, as they promote and maintain differentiation and support coculture systems. They need further development and validation for their successful implementation in toxicity testing in industry. Analytical measures also need to be implemented to enable compound exposure and metabolism measurements for in vitro to in vivo extrapolation. The future of SCD toxicological tests will combine advanced cell culture technologies and biokinetic measurements to support regulatory and research applications. However, scientific and technical hurdles must be overcome before SCD in vitro methods undergo appropriate validation and become accepted in the regulatory arena.
    01A - Beitrag in wissenschaftlicher Zeitschrift