Article
Multidisciplinary Sciences
Eric Simon, Maciej Motyka, Grietje H. Prins, Mei Li, Werner Rust, Stefan Kauschke, Coralie Viollet, Peter Olinga, Anouk Oldenburger
Summary: There is a need for predictive ex vivo models for NAFLD. This study profiles a new human and mouse PCLSs based assay for steatosis in NAFLD using RNASeq. Steatosis is induced by incremental supplementation of sugars, insulin, and fatty acids, and the gene expression regulation is analyzed across different nutrient conditions and time for both human and mouse liver organ derived PCLSs.
Article
Nutrition & Dietetics
Grietje H. Prins, Melany Rios-Morales, Albert Gerding, Dirk-Jan Reijngoud, Peter Olinga, Barbara M. Bakker
Summary: Butyrate has limited impact on the liver in an ex vivo induced MAFLD model, as it does not directly increase lipid beta-oxidation but may help prevent disease progression to NASH and cirrhosis.
Article
Multidisciplinary Sciences
Jae Hun Kim, Niccole Schaible, Joseph K. Hall, Erzsebet Bartolak-Suki, Yuqing Deng, Jacob Herrmann, Adam Sonnenberg, Holger P. Behrsing, Kenneth R. Lutchen, Ramaswamy Krishnan, Bela Suki
Summary: By measuring tissue stiffness at both the tissue and alveolar scales, we found that the lung tissue of patients with emphysema was 50% softer due to microscopic septal wall remodeling and structural deterioration. Protein expression profiling revealed a wide range of enzymes involved in septal wall remodeling, along with mechanical forces, leading to rupture and structural deterioration of the emphysematous lung parenchyma.
Article
Toxicology
Roberta Bartucci, Alex Z. van der Meer, Ykelien L. Boersma, Peter Olinga, Anna Salvati
Summary: Testing different nanomaterials on murine liver tissue slices showed that exposure to amino-modified polystyrene nanoparticles in serum-free conditions induced strong inflammation, while no inflammation was observed under serum-supplemented conditions. No clear signs of inflammation or fibrosis were detected after exposure to silica, titania, or carboxylated polystyrene in all tested conditions. These results indicate that tissue responses to nanoparticles can be strongly affected by exposure conditions and the ageing of nanoparticle dispersions.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Food Science & Technology
Amanda Lopes Hasuda, Elodie Person, Abdullah Khan Khoshal, Sandrine Bruel, Sylvie Puel, Isabelle P. Oswald, Ana Paula F. R. L. Bracarense, Philippe Pinton
Summary: Research indicates that Deoxynivalenol has toxic effects on liver cell lines and whole liver tissues, with the pig precision-cut liver slices model being a relevant and sensitive model for studying the liver toxicity of food contaminants.
FOOD AND CHEMICAL TOXICOLOGY
(2022)
Article
Pathology
Eike B. Preuss, Stephanie Schubert, Christopher Werlein, Helge Stark, Peter Braubach, Anne Hoefer, Edith K. J. Plucinski, Harshit R. Shah, Robert Geffers, Katherina Sewald, Armin Braun, Danny D. Jonigk, Mark P. Kuehnel
Summary: This study provides a comprehensive overview of the histomorphologic and pathologic changes during long-term cultivation of human precision-cut lung slices (PCLS). The results show that while the viability of PCLS is well preserved during long-term cultivation, there is a continuous loss of cells. The integrity of the alveoli is preserved for about 2 weeks, but the vasculatory system experiences significant loss of integrity within the first week. Ciliary beat in the small airways gradually decreases after 1 week, and keratinizing squamous metaplasia of the alveolar epithelium increases over time. Transcriptome analysis reveals an increased immune response and decreased metabolic activity within the first 24 hours after PCLS generation.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Multidisciplinary Sciences
S. J. Chidlow, L. E. Randle, R. A. Kelly
Summary: Precision cut liver slices are a promising ex vivo method for studying liver disease and drug induced liver injury. However, their application is limited by the availability of healthy human tissue and experimental variability. This study uses mathematical modeling to predict the generation of a desired oxygen gradient in precision cut liver slices.
Article
Immunology
Nina Cramer, Marie Luise Nawrot, Lion Wege, Marie Dorda, Charline Sommer, Olga Danov, Sabine Wronski, Armin Braun, Danny Jonigk, Sebastian Fischer, Antje Munder, Burkhard Tuemmler
Summary: Chronic respiratory infections with Pseudomonas aeruginosa have a significant impact on the quality of life and prognosis of cystic fibrosis patients. This study investigates the extent to which P. aeruginosa adapts to the CF airways and its influence on the fitness of the pathogen in the lungs. The results suggest that the severity of CF lung disease drives the adaptation of P. aeruginosa more strongly than the bacterial genotype.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Maggie Lam, Emma Lamanna, Louise Organ, Chantal Donovan, Jane E. E. Bourke
Summary: Precision cut lung slices (PCLS) are powerful experimental tools for respiratory research. They have been used to visualize airway and pulmonary artery contractility, assess bronchodilators and vasodilators, and measure disease-related outcomes in various species, including humans. This review highlights the established and innovative uses of PCLS as an intermediary between cellular and organ-based studies, and emphasizes their potential in investigating mechanisms and therapeutic targets for airway contraction and fibrosis in lung diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Toxicology
R. E. H. Karsten, N. J. W. Krijnen, W. Maho, H. Permentier, E. Verpoorte, P. Olinga
Summary: This study developed a mouse precision-cut liver slice model to study drug-induced cholestasis and assess its development. The findings show that cholestatic drugs increased intracellular bile-acid concentration and modulated bile-transporter genes. Chlorpromazine induced the most pronounced cholestasis and exhibited some transition into fibrosis.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Medicine, General & Internal
Ravi Jagatia, Ewald J. Doornebal, Una Rastovic, Nicola Harris, Moyosoreoluwa Feyide, Anabel Martinez Lyons, Rosa Miquel, Yoh Zen, Ane Zamalloa, Farooq Malik, Andreas Prachalias, Krishna Menon, Luke Boulter, Simon Eaton, Nigel Heaton, Sandra Phillips, Shilpa Chokshi, Elena Palma
Summary: In this study, patient-specific immunocompetent disease models of primary liver cancer (PLC) were created using precision-cut tissue slices (PCTS) derived from resected tumors, which effectively captured the multifaceted and intricate heterogeneity of the tumor and its microenvironment. The PCTS model maintained tissue architecture and tumor-specific immunophenotype, making it a robust preclinical tool for investigating immunotherapeutic drug efficacy and non-responsiveness.
Article
Engineering, Biomedical
Rachel Blomberg, Kayla Sompel, Caroline Hauer, Alex J. Smith, Brisa Pena, Jennifer Driscoll, Patrick S. Hume, Daniel T. Merrick, Meredith A. Tennis, Chelsea M. Magin
Summary: Lung cancer, the leading cause of cancer-related deaths worldwide, still occurs in people who have quit smoking. Researchers have developed an in vitro model of lung cancer premalignancy using precision-cut lung slices embedded in hydrogel and exposed to a cigarette smoke carcinogen. This model provides a foundation for studying the earliest stages of lung carcinogenesis and potential chemoprevention strategies.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Engineering, Biomedical
Nafiseh Rafiei, Mohammadamir G. Moghadam, Aaron Au, Romario Regeenes, Subbulakshmi Chidambaram, Tao Liang, Yufeng Wang, Christopher M. Yip, Herbert Gaisano, Jonathan Rocheleau
Summary: This article introduces a versatile microfluidic device for 3D fluorescence imaging of mouse or human pancreas PCTs, positioning them within a chamber with tall channels for media exchange. The device localizes shear stress to small regions on tissue surfaces and allows for controlled media exchange at lower flowrates than conventional chambers. It enables high-resolution imaging of immunofluorescently labeled PCTs on a confocal and with a large field of view on a SPIM without compromising image quality.
Article
Medicine, General & Internal
Mitchel J. R. Ruigrok, Khaled E. M. El Amasi, Diana J. Leeming, Jannie M. B. Sand, Henderik W. Frijlink, Wouter L. J. Hinrichs, Peter Olinga
Summary: IPF is a chronic lung disease with an urgent need for more effective drugs, with HSP47 identified as a potential therapeutic target. Targeted siRNA therapy against Serpinh1 showed reduction in fibronectin secretion in fibrotic lung slices, indicating a promising approach for fibrosis treatment.
FRONTIERS IN MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Amanda Lopes Hasuda, Elodie Person, Abdullah Khoshal, Sandrine Bruel, Sylvie Puel, Isabelle P. Oswald, Ana Paula F. R. L. Bracarense, Philippe Pinton
Summary: Emerging mycotoxins, including Beauvericin (BEA), enniatins (ENNs), emodin (EMO), apicidin (API), and aurofusarin (AFN), are frequently found contaminating food and there is growing interest in studying their impact on the liver. An ex vivo model and a human liver cell line were used to investigate the morphological and transcriptional changes caused by acute exposure to these mycotoxins. The results showed that most of these mycotoxins were cytotoxic to the cells and had the potential to be hepatotoxic, except for AFN.
Review
Medicine, General & Internal
L. Leonie van Leeuwen, Henri G. D. Leuvenink, Peter Olinga, Mitchel J. R. Ruigrok
Summary: Efforts have been made to address the demand for donor kidneys by using kidneys from donation after circulatory death donors. However, these kidneys are more prone to develop interstitial fibrosis and tubular atrophy due to severe ischemia and reperfusion injury. Current treatments, including machine perfusion, are unable to effectively ameliorate interstitial fibrosis and tubular atrophy. In this review, the authors propose a new therapeutic approach that supplements machine perfusion solutions with anti-fibrotic compounds. Several compounds, including LY2109761, galunisertib, imatinib, nintedanib, and butaprost, have shown promising anti-fibrotic effects and are considered excellent candidates for further ex vivo machine perfusion studies.
FRONTIERS IN MEDICINE
(2022)
Article
Toxicology
C. Biel, O. Martinec, B. Sibering, K. van Summeren, A. M. A. Wessels, D. J. Touw, K. P. de Jong, V. E. de Meijer, K. N. Faber, J. P. Ten Klooster, I. A. M. de Graaf, P. Olinga
Summary: In this study, using two different organoid culture media, the viability of human Precision-cut intestinal slices (hPCIS) was successfully extended to 72 hours, and the stem cells or enterocytes were specifically guided to regain their original function, metabolism, and proliferation. This is of great significance for pharmacokinetic and toxicology studies.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Gastroenterology & Hepatology
Su Suriguga, Mei Li, Theerut Luangmonkong, Miriam Boersema, Koert P. de Jong, Dorenda Oosterhuis, A. R. Gorter, Leonie Beljaars, Peter Olinga
Summary: This study compared the differences in inflammatory responses between cirrhotic and healthy livers using precision-cut liver slices (PCLSs). The results showed that cirrhotic PCLSs exhibited excessive inflammatory response and released less anti-inflammatory cytokines in response to LPS, which may contribute to the development of acute-on-chronic liver failure.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Toxicology
R. E. H. Karsten, N. J. W. Krijnen, W. Maho, H. Permentier, E. Verpoorte, P. Olinga
Summary: This study developed a mouse precision-cut liver slice model to study drug-induced cholestasis and assess its development. The findings show that cholestatic drugs increased intracellular bile-acid concentration and modulated bile-transporter genes. Chlorpromazine induced the most pronounced cholestasis and exhibited some transition into fibrosis.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Nataly Puerta Cavanzo, Sophie A. Riesmeijer, Iris L. Holt-Kedde, Paul M. N. Werker, Bram Piersma, Peter Olinga, Ruud A. Bank
Summary: Verteporfin (VP) has strong anti-fibrotic properties, inhibiting the differentiation of fibroblasts into myofibroblasts and reversing the activation status of fibroblasts. It may play an important role in the treatment of Dupuytren's disease.
SCIENTIFIC REPORTS
(2022)
Article
Immunology
Iris E. M. de Jong, Silke B. Bodewes, Otto B. van Leeuwen, Dorenda Oosterhuis, Veerle A. Lantinga, Adam M. Thorne, Bianca Lascaris, Marius C. van den Heuvel, Rebecca G. Wells, Peter Olinga, Vincent E. de Meijer, Robert J. Porte
Summary: This study found that the chemical composition of bile during NMP is closely related to the viability of the bile ducts, and that the bile ducts of high-risk human donor livers already undergo repair during NMP.
Article
Biochemistry & Molecular Biology
Theerut Luangmonkong, Pittaya Puphancharoensuk, Varisara Tongsongsang, Peter Olinga, Warisara Parichatikanond
Summary: Cycloastragenol, extracted from the traditional Chinese medicine Astragalus membranaceus, was found to delay liver fibrosis progression, protect the liver from damage, and promote hepatocyte regeneration.
Article
Biochemistry & Molecular Biology
Yana Geng, Johanna C. Arroyave-Ospina, Manon Buist-Homan, Josee Plantinga, Peter Olinga, Dirk -Jan Reijngoud, Frederike G. I. Van Vilsteren, Hans Blokzijl, Jan A. . A. . M. Kamps, Han Moshage
Summary: This study found that oleic acid induces necrotic cell death in liver sinusoidal endothelial cells (LSECs) but not in human umbilical vein endothelial cells (HUVECs). The toxicity of oleic acid can be attenuated by stimulating triglyceride synthesis. The toxicity is characterized by mitochondrial dysfunction and necrotic cell death. HUVECs are not suitable as a substitute model for LSECs.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Eric Simon, Maciej Motyka, Grietje H. Prins, Mei Li, Werner Rust, Stefan Kauschke, Coralie Viollet, Peter Olinga, Anouk Oldenburger
Summary: There is a need for predictive ex vivo models for NAFLD. This study profiles a new human and mouse PCLSs based assay for steatosis in NAFLD using RNASeq. Steatosis is induced by incremental supplementation of sugars, insulin, and fatty acids, and the gene expression regulation is analyzed across different nutrient conditions and time for both human and mouse liver organ derived PCLSs.
Review
Oncology
Herman J. Woerdenbag, Peter Olinga, Ellen A. Kok, Donald A. P. Brugman, Ulrike F. van Ark, Arwin S. Ramcharan, Paul W. Lebbink, Frederik J. H. Hoogwater, Daan G. Knapen, Derk Jan A. de Groot, Maarten W. Nijkamp
Summary: The use of cannabis products in oncology has generated interest, particularly among patients. However, the value of these products in cancer care and the associated risks are still a matter of debate despite the availability of research data. This review aims to provide a recommendation on the use of cannabis products in clinical oncology by assessing recent literature. The different types, characteristics, quality, and pharmacology of cannabis products are discussed. Standardization is crucial for ensuring reliable and reproducible quality. The oromucosal/sublingual route of administration is preferred over inhalation and drinking tea. Cannabinoids may interact with anticancer drugs and symptom management drugs, potentially enhancing or reducing their effects. Clinical research is needed to support the use, or refraining from use, of cannabis products in cancer patients.
Article
Cell Biology
Yana Geng, Junyu Wang, Sandra Alejandra Serna-Salas, Alejandra Hernandez Villanueva, Manon Buist-Homan, Marco Arrese, Peter Olinga, Hans Blokzijl, Han Moshage
Summary: Liver fibrosis is a response of the liver to chronic inflammation. Hepatic stellate cells (HSCs) can induce the inflammatory phenotype in liver macrophages (KCs) through the release of extracellular vesicles (EVs), thereby promoting fibrosis. This effect is mediated by the activation of Toll-like receptor 4 (TLR4) signaling pathway.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Cell Biology
Adhyatmika Adhyatmika, Kurnia S. S. Putri, Emilia Gore, Keri A. Mangnus, Catharina Reker-Smit, Detlef Schuppan, Leonie Beljaars, Peter Olinga, Barbro N. Melgert
Summary: This study found that IL13 induces the release of OPG in liver tissue through a TGF-beta-dependent pathway. The production of IL13 and subsequent OPG is mediated by the activation of IL13 receptors alpha 1 and alpha 2, as well as the transcription factors STAT6 and AP1.
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Mei Li, Vincent de Meijer, Peter Olinga, Anika Nagelkerke, Yana Geng
JOURNAL OF HEPATOLOGY
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Ke Luo, Yana Geng, Vincent de Meijer, Dorenda Oosterhuis, Peter Olinga
JOURNAL OF HEPATOLOGY
(2022)
Meeting Abstract
Gastroenterology & Hepatology
Yana Geng, Manon Buist-Homan, Peter Olinga, Hans Blokzijl, Han Moshage
Article
Toxicology
Kathryn Page, Walter Westerink, Kristie Sullivan, Thomas McDonald, Clive Roper
Summary: This study developed a new method to assess the skin irritation of antimicrobial cleaning products. The method utilized a more human-like model and demonstrated its effectiveness through comparison with in vivo rabbit skin irritation data.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Arupam Patra, Thirukumaran Kandasamy, Siddhartha Sankar Ghosh, Gurvinder Kaur Saini
Summary: This study successfully produced recombinant anisoplin and demonstrated its significant anti-cancer effect and ability to induce apoptosis in breast cancer cells. The activation of related signaling pathways may be the key to cell death.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Thomas Haller, Alexander Jesacher, Alberto Hidalgo, Christina Schmidt
Summary: This study used live cell imaging to observe the accumulation of amiodarone in primary rat alveolar type II cells, and found that it specifically accumulates in lamellar bodies. The uptake is rapid, while storage is persistent. The main mechanisms for intracellular bioaccumulation of amiodarone are proposed to be passive diffusion, ion-trapping, and lipophilic interactions.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Filiz Bakar-Ates, Erva Ozkan
Summary: This study investigated the ferroptotic effect of CuB in breast cancer cells and evaluated its combination with erastin, a ferroptosis inducer. The results showed that the combination treatment significantly activated the ferroptotic pathways and altered the expression of iron-related proteins in breast cancer cells.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Rachel Z. Bennie, Ian C. Shaw
Summary: Estrogen mimics are synthetic and naturally occurring compounds that can interact with estrogen receptors in animals. In vitro transactivation reporter gene assay and in silico molecular modelling can be used to predict the mimicry of these compounds, reducing reliance on animal studies.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Sevda Isik, Semra Cicek
Summary: This study found that high doses of riboflavin can cause cytotoxicity in rainbow trout gonad cells and affect the transcriptional expressions of antioxidant enzymes and growth and reproductive genes, potentially leading to DNA damage and cell death.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Ying Wang, Jie Wu, Mengqi Wan, Dou Yang, Fasheng Liu, Kehao Li, Manxin Hu, Yuanyuan Tang, Huiqiang Lu, Shouhua Zhang, Yuanzhen Xiong
Summary: m-Cresol is commonly used as an intermediate for pesticides and other industrial applications. This study investigated the hepatotoxicity of m-cresol using zebrafish larvae and explored its molecular mechanisms. The results suggest that m-cresol may induce liver damage in zebrafish larvae through oxidative stress and cell apoptosis pathways.
TOXICOLOGY IN VITRO
(2024)
Article
Toxicology
Vincent J. Manna, Shannon Dwyer, Vanessa Pizutelli, Salvatore J. Caradonna
Summary: The widespread use of electronic cigarettes and the emergence of a new illness have raised concerns about the effects of e-cigarette vapor on respiratory tissues. Researchers have developed a simple device to mimic the response of human airway tissue after long-term exposure to e-cigarette vapor, and have identified differences in the effects of different vapor compositions on airway tissue.
TOXICOLOGY IN VITRO
(2024)
