title: 3D pulmospheres serve as a personalized and predictive multicellular model for assessment of antifibrotic drugs.
abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal progressive fibrotic lung disease characterized by the presence of invasive myofibroblasts in the lung. Currently, there are only two FDA-approved drugs (pirfenidone and nintedanib) for the treatment of IPF. There are no defined criteria to guide specific drug therapy. New methodologies are needed not only to predict personalized drug therapy, but also to screen novel molecules that are on the horizon for treatment of IPF. We have developed a model system that exploits the invasive phenotype of IPF lung tissue. This ex vivo 3D model uses lung tissue from patients to develop pulmospheres. Pulmospheres are 3D spheroids composed of cells derived exclusively from primary lung biopsies and inclusive of lung cell types reflective of those in situ, in the patient. We tested the pulmospheres of 20 subjects with IPF and 9 control subjects to evaluate the responsiveness of individual patients to antifibrotic drugs. Clinical parameters and outcomes were also followed in the same patients. Our results suggest that pulmospheres simulate the microenvironment in the lung and serve as a personalized and predictive model for assessing responsiveness to antifibrotic drugs in patients with IPF.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Ranu
authors.initials: R
authors.lastname: Surolia
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Fu Jun
authors.initials: FJ
authors.lastname: Li
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Huashi
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Tracy
authors.initials: T
authors.lastname: Luckhardt
authors.affiliation: Division of Preventative Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Sejong
authors.initials: S
authors.lastname: Bae
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Rui-Ming
authors.initials: RM
authors.lastname: Liu
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Sunad
authors.initials: S
authors.lastname: Rangarajan
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.|Birmingham VA Medical Center, Birmingham, Alabama, USA.
authors.forename: Joao
authors.initials: J
authors.lastname: de Andrade
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.|Birmingham VA Medical Center, Birmingham, Alabama, USA.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Thannickal
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine and.
authors.forename: Veena B
authors.initials: VB
authors.lastname: Antony
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008954:Models, Biological; D058628:Myofibroblasts / Q000187:drug effects*; D057285:Precision Medicine; D011728:Pyridones / Q000494:pharmacology* / Q000627:therapeutic use; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007211:Indoles; D011728:Pyridones; D053773:Transforming Growth Factor beta1; C093844:pirfenidone; C530716:nintedanib