Human-Based Advanced in vitro Approaches to Investigate Lung Fibrosis and Pulmonary Effects of COVID-19

Frontiers in Medicine Mirjam Kiener, Nuria Roldan, Carlos Machahua, Arunima Sengupta, Thomas Geiser, Olivier Thierry Guenat, Manuela Funke-Chambour, Nina Hobi and Marianna Kruithof-de Julio Abstract The coronavirus disease 2019 (COVID-19) pandemic has caused considerable socio-economic burden, which fueled the development of treatment strategies and vaccines at an unprecedented speed. However, our knowledge on disease recovery

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Modelling alveoli on a breathing lung-on-chip in health and disease

European Respiratory Journal Clementine Richter, Alberto Hidalgo, Patrick Carius, Nuria Roldan, Janick Stucki, Nina Hobi, Nicole Schneider-Daum, Calus-Michael Lehr Abstract The pharmaceutical industry is in rising need for alternative methods that minimise animal testing during early drug development, mainly because of the poor transferability from animal to human, costs or ethical issues. However, traditional cellular models fail to reproduce essential physio-pathological, systemic and structural aspects. In this sense, organ-on-chips have

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Organoids and lung-on-chip to study SARS-CoV-2-mediated lung injury

European Respiratory Journal Mirjam Kiener, Lea De Maddalena, Nuria Roldan, George N. Thalmann, Thomas Geiser, Nina Hobi, Marianna Kruithof-De Julio Abstract COVID-19 is an infectious disease caused by the newly discovered coronavirus named SARS-CoV-2. The virus enters the body through the airways by exploiting the angiotensin-converting enzyme 2 (ACE2) and serine proteinase TMPRSS2. Thus, especially lung epithelial cells are attacked by the virus. In the distal lung, the

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Interleukin-2 – induced vascular leak syndrome: clinically relevant in vitro recapitulation with a patient-derived lung-on-chip

European Respiratory Journal Giulia Raggi, Nuria Roldan, Virginie Micallef, Aude Rapet, Lea De Maddalena, Théo Imler, Laurène Froment, Thomas M. Marti, Ralph A. Schmid, Ekaterina Breous-Nystrom, Adrian B. Roth, Lauriane Cabon, Nina Hobi Abstract Systemic administration of Interleukin-2 (IL-2) at high doses in cancer immunotherapy has been associated with vascular leak syndrome (VLS) and pulmonary edema, a life-threatening condition. The complex mechanism of action underlying this medication’s adverse event is not yet well understood, however it has been proposed to

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Modeling alveolar barrier disruption in vitro for sepsis-induced ARDS preclinical studies

European Respiratory Journal Nuria Roldan, Giulia Raggi, Kleanthis Fytianos, Jessica Petracca, Janick Stucki, Fabian Käsermann, Nina Hobi Abstract Disruption of the alveolar barrier is one of the main features of Acute Respiratory Distress Syndrome (ARDS), a devastating disease with no pharmacological treatments available at present. Sepsis is also a common risk factor for the development of ARDS, associated with 30% of the cases. During sepsis, hemolysis takes place,

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Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Frontiers in Physiology Kirsten Sehlmeyer, Jannik Ruwisch, Nuria Roldan, and Elena Lopez-Rodriguez Abstract Surfactant protein C (SP-C) is an important player in enhancing the interfacial adsorption of lung surfactant lipid films to the alveolar air-liquid interface. Doing so, surface tension drops down enough to stabilize alveoli and the lung, reducing the work of breathing. In

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CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

AJP Lung Cell and Molecular Physiology Limei Wang, Patrick Dorn, Soheila Zeinali, Laurène Froment, Sabina Berezowska, Gregor J. Kocher, Marco P. Alves, Melanie Brügger, Blandina I. O. Esteves, Fabian Blank, Carlos Wotzkow, Selina Steiner, Mario Amacker, Ren-Wang Peng, Thomas M. Marti, Olivier T. Guenat, Peter K. Bode, Ueli Moehrlen, Ralph A. Schmid, and Sean R.

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Clinically relevant tissue scale responses as new readouts from organs-on-a-chip for precision medicine

Annual Review of Analytical Chemistry Olivier T. Guenat, Thomas Geiser & François Berthiaume  Abstract Organs-on-chips (OOC) are widely seen as being the next generation in vitro models able to accurately recreate the biochemical-physical cues of the cellular microenvironment found in vivo. In addition, they make it possible to examine tissue-scale functional properties of multicellular systems

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Azithromycin has enhanced effects on lung fibroblasts from idiopathic pulmonary fibrosis (IPF) patients compared to controls

Respiratory Research  Kristina Krempaska, Sandra Barnowski, Jacopo Gavini, Nina Hobi, Simone Ebener, Cedric Simillion, Andrea Stokes, Ronja Schliep, Lars Knudsen, Thomas K. Geiser & Manuela Funke-Chambour  Abstract Background. Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease without a cure and new drug strategies are urgently needed. Differences in behavior between diseased and healthy

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