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
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
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
Respiratory System
Sarah Marie Nussbaum, Julia Krabbe, Svenja Boell, Aaron Babendreyer, Christian Martin
Summary: The study successfully established a model of long-term cultivated rat PCLS for 29 days with sustained viability, but observed cellular changes and alterations in gene expression during long-term cultivation. Further investigations are needed before long-term cultivated PCLS can be used for in-depth study of chronic diseases and chronic toxicity.
RESPIRATORY RESEARCH
(2022)
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
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
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
Immunology
Kasin Yadunandam Anandam, Cilia Abad, Tetiana Synova, Mireia Vinas-Noguera, Bahareh Bolboli, Ivan Vokral, Rona Karahoda, Frantisek Staud
Summary: Maternal inflammation during pregnancy is a major feature of several pregnancy complications and is a significant risk factor for neurodevelopmental and neuropsychiatric disorders in the offspring. The placenta, as the interface between the mother and the fetus, plays a crucial role in fetal development and immune regulation. The use of placental slices as a model helps in studying the acute inflammatory response and the role of sexual dimorphism in this process.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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
Toxicology
Lina Agren, Linda Elfsmark, Christine Akfur, Sofia Jonasson
Summary: Exposure to NH3 can cause concentration-dependent cytotoxic effects and lung damages. The study established an in vitro model using Precision-cut Lung Slices (PCLS) to identify new medical treatments and biomarkers. Different treatment strategies were evaluated, but none of them reduced cytotoxicity, indicating the potential of the PCLS method for future research.
TOXICOLOGY LETTERS
(2021)
Article
Agriculture, Dairy & Animal Science
V Filor, B. Seeger, N. de Buhr, M. von Koeckritz-Blickwede, M. Kietzmann, H. Oltmanns, J. Meissner
Summary: Mastitis in cattle is a significant health problem in the dairy industry. This study used precision-cut bovine udder slices (PCBUS) to investigate the immune response and bacterial invasion during bovine mastitis. The results showed similarities between PCBUS and primary bovine mammary epithelial cells, supporting the use of PCBUS for further understanding of the pathophysiological processes and alternative therapies for mastitis.
JOURNAL OF DAIRY SCIENCE
(2022)
Article
Respiratory System
Muzamil Majid Khan, Daniel Poeckel, Aliaksandr Halavatyi, Joanna Zukowska-Kasprzyk, Frank Stein, Johanna Vappiani, Daniel C. Sevin, Christian Tischer, Nico Zinn, Jessica D. Eley, Natasja Staehr Gudmann, Thomas Muley, Hauke Winter, Andrew J. Fisher, Carmel B. Nanthakumar, Giovanna Bergamini, Rainer Pepperkok
Summary: Fibrosis can lead to tissue architecture and function loss in any organ, characterized by excessive deposition of extracellular matrix proteins, but the lack of suitable human models and techniques hinders the discovery of cures. The study demonstrates the viability and metabolic activity of human precision-cut lung slices (hPCLS) in ex vivo culture, showing an induction of ECM proteins related to pulmonary fibrosis without increased fibrillar collagen deposition. The presence of pro-ECM degradation activity in hPCLS cultures suggests potential for testing anti-fibrotic agents.
EUROPEAN RESPIRATORY JOURNAL
(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.
Article
Gastroenterology & Hepatology
Joachim H. Mortensen, Wouter T. van Haaften, Morten A. Karsdal, Anne-Christine Bay-Jensen, Peter Olinga, Henning Gronbaek, Christian L. Hvas, Tina Manon-Jensen, Gerard Dijkstra, Anders Dige
Summary: The study suggests that VICM biomarker decreases over time in CD patients responding to anti-TNF alpha treatment, and may serve as a marker for monitoring early response to treatment.
JOURNAL OF CLINICAL GASTROENTEROLOGY
(2021)
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)
