Prof. Mateja Erdani Kreft is Full Professor of Cell Biology at the Faculty of Medicine, University of Ljubljana, where she also serves as Head of the Laboratory for Cell and Tissue Culture. She leads the national research programme P3-0108 (Cell Biology and Molecular Genetics in Biomedicine) and coordinates collaborative projects with industry. She has made pioneering contributions to the development of advanced biomimetic 2D and 3D in vitro models, establishing methodologies that bridge fundamental research and translational applications, and has several patent-protected innovations in this area. Her current research focuses on basic cell biology, the therapeutic potential of the human amniotic membrane, and the role of tunnelling nanotubes in cancer, and she is internationally recognised for her expertise in electron microscopy, freeze-fracture immunolabeling, and correlative microscopy techniques, which she applies to investigate subcellular structures and drug responses in biomimetic models. She actively supports students in achieving research excellence, is co-author of the monograph Biology of Bladder Cancer (Springer, 2024), serves on the editorial boards of Histochemistry and Cell Biology and Scientific Reports, and in recognition of her scientific leadership and innovation, she received the University of Ljubljana Award for Outstanding Research Achievements in 2024.Prof. Mateja Erdani Kreft is Full Professor of Cell Biology at the Faculty of Medicine, University of Ljubljana, where she also serves as Head of the Laboratory for Cell and Tissue Culture. She leads the national research programme P3-0108 (Cell Biology and Molecular Genetics in Biomedicine) and coordinates collaborative projects with industry. She has made pioneering contributions to the development of advanced biomimetic 2D and 3D in vitro models, establishing methodologies that bridge fundamental research and translational applications, and has several patent-protected innovations in this area. Her current research focuses on basic cell biology, the therapeutic potential of the human amniotic membrane, and the role of tunnelling nanotubes in cancer, and she is internationally recognised for her expertise in electron microscopy, freeze-fracture immunolabeling, and correlative microscopy techniques, which she applies to investigate subcellular structures and drug responses in biomimetic models. She actively supports students in achieving research excellence, is co-author of the monograph Biology of Bladder Cancer (Springer, 2024), serves on the editorial boards of Histochemistry and Cell Biology and Scientific Reports, and in recognition of her scientific leadership and innovation, she received the University of Ljubljana Award for Outstanding Research Achievements in 2024.
Oxidative stress-induced inflammation in an in vitro model of interstitial cystitis/bladder pain syndrome is mitigated by human amniotic membrane
Tadeja Kuret PhD1, Eva Boc2, Aleksandar Janev PhD1, Peter Veranič PhD1, Mateja Erdani Kreft PhD1.
1Institute of Cell Biology, University of Ljubljana, Faculty of Medicine, Ljubljana, Slovenia; 2University of Ljubljana, Biotechnical Faculty, Ljubljana, Slovenia
Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, noninfectious bladder disorder of unknown aetiology, characterised by urothelial barrier dysfunction, oxidative stress, and inflammation [1-2]. Current therapies are often ineffective, highlighting the need for novel models and therapeutic approaches. We aimed to establish a human in vitro IC/BPS model to explore molecular mechanisms driving disease and evaluate the therapeutic potential of the human amniotic membrane (hAM), known for its regenerative, anti-inflammatory and immunomodulatory properties [3–6].
Methods: Normal human urothelial cells (SV-HUC1) were exposed to glucose oxidase (GO; 20 mU/ml) for 3 hours to induce peak oxidative stress, or for 24 hours to model prolonged oxidative stress and inflammation [7]. To assess the therapeutic effect of hAM, cells were incubated with hAM during an additional 24-hour exposure to GO. mRNA expression was evaluated by qPCR, while protein levels were assessed using ELISA, Western blotting, and immunofluorescence. Statistical significance was determined using ANOVA. The preparation of hAM followed the recommendations of COST Action CA17111 [8].
Results: GO treatment induced a transient NRF2-mediated antioxidant response, with peak expression of NQO1 and SOD2 at 3 h, which declined by 24 h. Prolonged exposure led to activation of the JAK1/STAT1 pathway and enrichment of type I/II interferon signalling, accompanied by increased expression of selected interferon-stimulated genes and pro-inflammatory cytokines such as IL6 and CXCL8. hAM treatment significantly reduced the expression and secretion of inflammatory mediators, decreased phosphorylated JAK1 levels, restored SOD2 expression, and upregulated the epithelial differentiation marker KRT13 and the tight junctional proteins, suggesting improved urothelial barrier function.
Conclusion: Our in vitro IC/BPS model recapitulates key pathological hallmarks of the disease, including transient NRF2-driven antioxidant activation and sustained JAK1/STAT1-mediated inflammatory signalling. Treatment with hAM attenuates oxidative stress and pro-inflammatory responses while promoting epithelial differentiation and junctional integrity, underscoring its potential as a multi-target therapeutic strategy for IC/BPS.
References
ARIS, P3-0108. ARIS, Z3-50118.
[1] Interstitial Cystitis, Bladder Pain Syndrome, Oxidative Stress, Human Amniotic Membrane, Urothelial Cells, Inflammation