PMID- 34026781 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231102 IS - 2296-858X (Print) IS - 2296-858X (Electronic) IS - 2296-858X (Linking) VI - 8 DP - 2021 TI - Human-Based Advanced in vitro Approaches to Investigate Lung Fibrosis and Pulmonary Effects of COVID-19. PG - 644678 LID - 10.3389/fmed.2021.644678 [doi] LID - 644678 AB - 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 is sparse and concerns about long-term pulmonary impairments are increasing. Causing a broad spectrum of symptoms, COVID-19 can manifest as acute respiratory distress syndrome (ARDS) in the most severely affected patients. Notably, pulmonary infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the causing agent of COVID-19, induces diffuse alveolar damage (DAD) followed by fibrotic remodeling and persistent reduced oxygenation in some patients. It is currently not known whether tissue scaring fully resolves or progresses to interstitial pulmonary fibrosis. The most aggressive form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF). IPF is a fatal disease that progressively destroys alveolar architecture by uncontrolled fibroblast proliferation and the deposition of collagen and extracellular matrix (ECM) proteins. It is assumed that micro-injuries to the alveolar epithelium may be induced by inhalation of micro-particles, pathophysiological mechanical stress or viral infections, which can result in abnormal wound healing response. However, the exact underlying causes and molecular mechanisms of lung fibrosis are poorly understood due to the limited availability of clinically relevant models. Recently, the emergence of SARS-CoV-2 with the urgent need to investigate its pathogenesis and address drug options, has led to the broad application of in vivo and in vitro models to study lung diseases. In particular, advanced in vitro models including precision-cut lung slices (PCLS), lung organoids, 3D in vitro tissues and lung-on-chip (LOC) models have been successfully employed for drug screens. In order to gain a deeper understanding of SARS-CoV-2 infection and ultimately alveolar tissue regeneration, it will be crucial to optimize the available models for SARS-CoV-2 infection in multicellular systems that recapitulate tissue regeneration and fibrotic remodeling. Current evidence for SARS-CoV-2 mediated pulmonary fibrosis and a selection of classical and novel lung models will be discussed in this review. CI - Copyright 2021 Kiener, Roldan, Machahua, Sengupta, Geiser, Guenat, Funke-Chambour, Hobi and Kruithof-de Julio. FAU - Kiener, Mirjam AU - Kiener M AD - Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. AD - Department for BioMedical Research DBMR, Urology Research Laboratory, University of Bern, Bern, Switzerland. AD - Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland. FAU - Roldan, Nuria AU - Roldan N AD - Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland. FAU - Machahua, Carlos AU - Machahua C AD - Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. AD - Department for BioMedical Research DBMR, Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Sengupta, Arunima AU - Sengupta A AD - Organs-on-Chip Technologies, ARTORG Center for Biomedical Engineering, University of Bern, Bern, Switzerland. FAU - Geiser, Thomas AU - Geiser T AD - Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. AD - Department for BioMedical Research DBMR, Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Guenat, Olivier Thierry AU - Guenat OT AD - Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. AD - Organs-on-Chip Technologies, ARTORG Center for Biomedical Engineering, University of Bern, Bern, Switzerland. AD - Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Funke-Chambour, Manuela AU - Funke-Chambour M AD - Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. AD - Department for BioMedical Research DBMR, Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Hobi, Nina AU - Hobi N AD - Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland. FAU - Kruithof-de Julio, Marianna AU - Kruithof-de Julio M AD - Department for BioMedical Research DBMR, Urology Research Laboratory, University of Bern, Bern, Switzerland. AD - Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland. AD - Organoid Core, Department for BioMedical Research, University of Bern, Bern, Switzerland. LA - eng PT - Journal Article PT - Review DEP - 20210507 PL - Switzerland TA - Front Med (Lausanne) JT - Frontiers in medicine JID - 101648047 PMC - PMC8139419 OTO - NOTNLM OT - COVID-19 OT - SARS-CoV-2 OT - alveolar regeneration OT - in vitro lung models OT - interstitial pulmonary fibrosis OT - lung-on-chip OT - organoids OT - precision-cut lung slices COIS- NR and NH are employed by AlveoliX AG. OG and TG are shareholder and in the scientific board of AlveoliX AG. MK and MK-dJ are collaborators of AlveoliX AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/25 06:00 MHDA- 2021/05/25 06:01 PMCR- 2021/05/07 CRDT- 2021/05/24 08:14 PHST- 2020/12/21 00:00 [received] PHST- 2021/04/01 00:00 [accepted] PHST- 2021/05/24 08:14 [entrez] PHST- 2021/05/25 06:00 [pubmed] PHST- 2021/05/25 06:01 [medline] PHST- 2021/05/07 00:00 [pmc-release] AID - 10.3389/fmed.2021.644678 [doi] PST - epublish SO - Front Med (Lausanne). 2021 May 7;8:644678. doi: 10.3389/fmed.2021.644678. eCollection 2021.