Amniotic Fluid Stem Cells from EGFP Transgenic Mice Attenuate Hyperoxia-Induced Acute Lung Injury

Shih-Tao Wen,Chih-Ching Yen,Cheng-Wei Lai,Chuan-Mu Chen,Hsiao-Ling Chen,Wei Chen,Shinn-Chih Wu,Kun-Hsiung Lee,Andreas Zirlik

doi:10.1371/journal.pone.0075383

Abstract

High concentrations of oxygen aggravate the severity of lung injury in patients requiring mechanical ventilation. Although mesenchymal stem cells have been shown to effectively attenuate various injured tissues, there is limited information regarding a role for amniotic fluid stem cells (AFSCs) in treating acute lung injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung injury in an experimental model of hyperoxia-induced lung injury. AFSCs were isolated from EGFP transgenic mice. The in vitro differentiation, surface markers, and migration of the AFSCs were assessed by specific staining, flow cytometry, and a co-culture system, respectively. The in vivo therapeutic potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung injury in mice. The administration of AFSCs significantly reduced the hyperoxia-induced pulmonary inflammation, as reflected by significant reductions in lung wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing the levels of inflammatory cytokine (IL-1β, IL-6, and TNF-α) and early-stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and engrafted into a peripheral lung epithelial cell lineage by fluorescence microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new therapeutic strategy for acute lung injury (ALI), for which efficient treatments are currently unavailable.

Highlights

Acute respiratory distress syndrome (ARDS) is a condition characterized by acute onset, bilateral lung infiltrates, refractory hypoxemia, and the absence of cardiogenic pulmonary edema
Supplemental oxygen can exacerbate the pathogenic processes within the lung [8,9], and this may result in hyperoxia-induced acute lung injury (ALI) [10,11], the pathological changes of which resemble ARDS in animal models [12]
We investigated whether murine amniotic fluid stem cells (AFSCs) from enhanced green fluorescent protein (EGFP) transgenic mice have beneficial effects on lung function and animal survival in a model of hyperoxia-induced ALI

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is a condition characterized by acute onset, bilateral lung infiltrates, refractory hypoxemia, and the absence of cardiogenic pulmonary edema. ARDS and acute lung injury (ALI) are major causes of mortality and morbidity in critically ill patients [1,2]. The acute exudative phase (the first 24-72 h) of ALI is characterized by infiltration of inflammatory cells and disruption of the alveolar–. Supplemental oxygen can exacerbate the pathogenic processes within the lung [8,9], and this may result in hyperoxia-induced ALI [10,11], the pathological changes of which resemble ARDS in animal models [12]. Therapeutic strategies for hyperoxia-induced ALI may be the same as for clinical ARDS. Despite decades of efforts to identify pharmacologic agents to treat ALI, there are still no effective therapeutic agents for this condition [13]

Methods

Results

Conclusion