Intravenous administration of adipose-derived stromal cells does not ameliorate bleomycin-induced lung injury in rats

Akira Nakada,Tatsuo Nakamura,Masato Uji

doi:10.4236/ojrm.2013.22007

Abstract

Background: Mesenchymal stromal cells (MSCs) have been studied intensively in regenerative medicine. Among MSCs, adipose tissue-derived stromal cells (ASCs) are relatively easy to obtain from a patient. Since ASCs are ideal candidates for use in the treatment of disease states including pulmonary fibrosis, we investigated whether intravenous injection of ASCs could exert a therapeutic effect against bleomycin-induced lung injury in rats. Methods: Rats were intratracheally administered bleomycin, and one week later ASCs were isolated and cultured. Two weeks after bleomycin treatment ASCs or PBS (phosphate-buffered saline) were injected to the rats. Three or six weeks after bleomycin instillation, the total cell counts and their profile in bronchoalveolar lavage fluid (BALF) were measured, and a histological evaluation was semi-quantitatively assessed for the injured lungs, followed by cell tracing. Results: The BALF cell counts and its profiles were not significantly different in the ASCs and PBS groups. Furthermore, ASC treatment led to no significant histological effect compared with the PBS treatment. Using a fluorescent cell tracer, it was noted that the ASCs homed to the injured lung areas, but some ASCs accumulated around scars, and scarcely migrated into the fibrotic areas. Conclusions: In the present study, the intravenous administration of ASCs could not reduce the severity of bleomycin-induced lung injury in a rat model. Although the ASC counts and passage numbers were suitable, the older age and fibrotic disease stage of the rats were likely responsible for the treatment failure.

Highlights

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal form of pulmonary fibrosis characterized by fibroblast proliferation, extracellular matrix deposition, and progressive lung scarring, and exhibits a histopathological pattern consistent with usual interstitial pneumonia (UIP) [1,2]
No significant differences in the total cell counts and cell profile in the bronchoalveolar lavage fluid (BALF) were observed among groups D, E and F
Semiquantitative Morphological Evaluation of the Lung Injury in Rats Treated with adipose tissue-derived stromal cells (ASCs) (Figure 2)

Summary

INTRODUCTION

Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal form of pulmonary fibrosis characterized by fibroblast proliferation, extracellular matrix deposition, and progressive lung scarring, and exhibits a histopathological pattern consistent with usual interstitial pneumonia (UIP) [1,2]. Recent data strongly suggest that the mechanisms driving IPF reflect abnormal, deregulated wound healing in response to multiple sites of ongoing alveolar epithelial injury, involving increased activity, and possibly exaggerated responses by a spectrum of proinflammatory and profibrogenic factors [3,4]. Most treatments, such as corticosteroids, and immunosuppressive, immunomodulatory, or antifibrotic agents, seek to suppress inflammation, but none has been proven to alter this process [5,6]. The purpose of this study was to examine whether ASC treatment could attenuate bleomycin-induced lung injury in rats

Bleomycin-Induced Lung Injury Model

Isolation and Culture of Rat ASCs

Experimental Groups

DiI and DAPI Staining

Preparation of the Lung Tissues and Histological Evaluation by the SMI

Statistical Analysis

RESULTS

DISCCUSION

CONCLUSION