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3D pulmospheres serve as a personalized and predictive multicellular model for assessment of antifibrotic drugs
Ranu Surolia, … , Victor J. Thannickal, Veena B. Antony
Ranu Surolia, … , Victor J. Thannickal, Veena B. Antony
Published January 26, 2017
Citation Information: JCI Insight. 2017;2(2):e91377. https://doi.org/10.1172/jci.insight.91377.
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Resource and Technical Advance Pulmonology Therapeutics

3D pulmospheres serve as a personalized and predictive multicellular model for assessment of antifibrotic drugs

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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

Ranu Surolia, Fu Jun Li, Zheng Wang, Huashi Li, Gang Liu, Yong Zhou, Tracy Luckhardt, Sejong Bae, Rui-ming Liu, Sunad Rangarajan, Joao de Andrade, Victor J. Thannickal, Veena B. Antony

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Figure 4

Modulation of invasiveness by treatment with TGF-β1 in control pulmosphere and with nintedanib in IPF pulmosphere.

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Modulation of invasiveness by treatment with TGF-β1 in control pulmosphe...
(A) Representative pulmosphere from control lung not treated and treated with TGF-β1. Scale bar: 250 μm. (B) Calculated zone of invasion (ZOI) from 5 lung pulmospheres from 9 controls not treated and treated with TGF-β1. Each dot represents the mean value of calculated ZOI from 5 pulmospheres for each control subject. Data are expressed as mean (error bars) ± SD. P = 0.002, compared with control pulmospheres (untreated), 2-tailed paired t test. (C) Representative phase-contrast images of pulmospheres from a patient with IPF not treated and treated with nintedanib (1 μM) for 12 hours. Scale bar: 250 μm. (D) Invasiveness of pulmospheres from an individual patient not treated and treated with nintedanib. Each dot represents one pulmosphere. Data are expressed as mean (error bars) ± SD. P = 0.002, compared with untreated pulmospheres, 2-tailed paired t test.

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