Human Adipose-derived Mesenchymal Stem Cells Attenuate Early Stage of Bleomycin Induced Pulmonary Fibrosis: Comparison with Pirfenidone
Reddy Manoj, Fonseca Lyle, Gowda Shashank, Chougule Basavraj, Hari Aarya, Totey Satish,
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( Reddy Manoj )
DIL Complex Kasiak Research Pvt Ltd
( Fonseca Lyle )
DIL Complex Kasiak Research Pvt Ltd
( Gowda Shashank )
DIL Complex Kasiak Research Pvt Ltd
( Chougule Basavraj )
DIL Complex Kasiak Research Pvt Ltd
( Hari Aarya )
DIL Complex Kasiak Research Pvt Ltd
( Totey Satish )
DIL Complex Kasiak Research Pvt Ltd
Abstract
Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible, invariably fatal fibrotic lung disease with no lasting option for therapy. Mesenchymal stem cells (MSCs) could be a promising modality for the treatment of IPF. Aim of the study was to investigate improvement in survivability and anti-fibrotic efficacy of human adipose-derived mesenchymal stem cells (AD-MSCs) in comparison with pirfenidone in the bleomycin-induced pulmonary fibrosis model.
Methods: Human AD-MSCs were administered intravenously on day 3, 6 and 9 after an intra-tracheal challenge with bleomycin, whereas, pirfenidone was given orally in drinking water at the rate of 100 mg/kg body weight three times a day daily from day 3 onward. AD-MSCs were labelled with PKH-67 before administration to detect engraftment. Disease severity and improvement was assessed and compared between sham control and vehicle control groups using Kaplan-Meier survival analysis, biochemical and molecular analysis, histopathology and high resolution computed tomography (HRCT) parameters at the end of study.
Results: Results demonstrated that AD-MSCs significantly increase survivability; reduce organ weight and collagen deposition better than pirfenidone group. Histological analyses and HRCT of the lung revealed that AD-MSCs afforded protection against bleomycin induced fibrosis and protect architecture of the lung. Gene expression analysis revealed that AD-MSCs potently suppressed pro-fibrotic genes induced by bleomycin. More importantly, AD-MSCs were found to inhibit pro-inflammatory related transcripts.
Conclusions: Our results provided direct evidence that AD-MSC-mediated immunomodulation and anti-fibrotic effect in the lungs resulted in marked protection in pulmonary fibrosis, but at an early stage of disease.
키워드
Idiopathic pulmonary fibrosis; Mesenchymal stem cells; Adipose tissue; Pirfenidone; Bleomycin; HRCT
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