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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 3

Quantitation of invasion in control and IPF patient pulmospheres.

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Quantitation of invasion in control and IPF patient pulmospheres.
(A) Im...
(A) Immunofluorescent staining for α smooth muscle actin (α-SMA) in control and IPF pulmospheres. Scale bar: 50 μm. (B) FACS analysis of cells of dissociated pulmospheres (n = 7) from 7 control subjects and 9 IPF patients. (C) α-SMA cells were significantly increased in IPF patient pulmospheres compared with control pulmospheres. Data are expressed as mean (error bars) ± SD. P = 0.005, compared with control subjects, 2-tailed unpaired Student’s t test. Each dot represents the value for an individual subject. (D) Illustration and calculation of 3D pulmosphere zone of invasion (ZOI). Schematic of pulmosphere after 12 hours of incubation in collagen gel matrix: the initial pulmosphere is delineated by a blue circle, the invading pulmosphere is delineated by dotted line covering the expanded area. (E) The formula to quantitate ZOI. (F) Differential ZOI in pulmospheres from controls (n = 9) and IPF patients (n = 20). Data are expressed as mean (error bars) ± SD. P = 0.03, compared with control subjects, Mann Whitney test. Each data point represents measurements of ZOI% from 5 pulmospheres from each individual control subject and IPF patient.

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ISSN 2379-3708

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