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TOPICAL COLLECTIONS

Methods for Lung Organoid Culture, Disease Modelling, and Regenerative Medicine 

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Vishwaraj Sontake

Vishwaraj Sontake

Duke University School of Medicine

Vishwaraj Sontake is a cell and molecular biologist with expertise in the field of lung injury, repair, and regeneration. Dr. Sontake earned his PhD from Osmania University, Hyderabad, India. He was awarded a CSIR (India’s top scientific board) research fellowship to pursue his doctoral degree at the National Institute of Nutrition (NIN), an Indian Council of Medical Research (ICMR) Institute. His doctoral work was focused on understanding the molecular mechanisms of chronic tissue remodeling diseases using lung and kidney as organ systems. During this time, he collaborated with researchers at Cincinnati children’s hospital medical center (CCHMC), University of Cincinnati, to uncover the role of fibrocytes in chronic fibrotic lung diseases such as idiopathic pulmonary fibrosis (IPF) and cystic fibrosis (CF). He also studied the role of the mesenchymal and mesothelial cells in IPF.   Sontake’s current research is focused on establishing lung organoid models for disease modeling and regenerative medicine. He uses human and mouse lungs to establish the organoids from various lung stem cells such as AT2, Basal, and Club cells. He is using organoid models to understand the cell-autonomous mechanisms that control stem cell fate. Additionally, he is developing methods to study the physical interactions between epithelial and fibroblasts in both in-vivo and in ex-vivo cultures. Dr. Sontake’s work has been published in many peer-reviewed journals, and he is an active member of the American Thoracic Society (ATS) and American Heart Association (AHA).

Collection Overview

Direct exposure of the lungs to the environment makes them suspectable to various injuries caused by toxic chemicals and microbial agents. Many of these injuries often lead to acute or chronic lung diseases such as COPD, Asthma, IPF, and ARDS. A great deal of work from mouse models has advanced our understanding of the repair and regeneration of the lung. Despite these advances, we currently do not have a complete understanding of complex cell-cell interactions and how they influence stem cell fate in normal, regenerating, and disease tissue. Studying these interactions in in-vivo models has been a major challenge because of the lack of tools and techniques. To overcome these limitations, organoid technology emerged as a great tool for disease modelling, studying cell-cell interaction, and therapeutic discovery.

The lung organoids can be generated from stem/progenitor cells from both airways and alveoli. However, the successful establishment of organoids starts with isolation of pure stem/progenitor population and is influenced by various factors such feeder cell type, type of scaffold required for 3D organization, growth conditions, and nutrient supplements. Variability in these factors often results in nonreproducible results.

This methods collection aims to establish a resource hub for researchers, which include detailed protocols for cell type isolation, establishment of epithelial cell-specific organoids, organoids for disease modelling, and protocols for gene manipulations in organoids. Besides, this methods collection will also accept manuscripts from topics such as long-term and short-term expansion of organoids, biobanking, and protocols for cell engraftment into mouse models.

Articles

Engineered Lung Tissues Prepared from Decellularized Lung Slices
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Engineered Lung Tissues Prepared from Decellularized Lung Slices

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Cited by 6

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2022

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Abstracts

Human lung bronchial organoids as disease model system for airway diseases

Sarah Miethe1

1Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, 6 Member of the German Center for Lung Research (DZL) and the Universities of Giessen and 7 Marburg Lung Center, Philipps University Marburg, Germany