Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in Idiopathic Pulmonary Fibrosis (IPF).
BACKGROUND
Experimental data have provided evidence that progenitor cells of bone marrow (BM) origin may play a role in the fibrogenic process of the lung.


OBJECTIVE
To probe the possible involvement of BM mesenchymal stem cells (MSCs) in the pathophysiology of Idiopathic Pulmonary Fibrosis (IPF) by investigating the molecular profile of these cells.


METHODS
BM MSCs were studied in 10 IPF patients and 10 healthy controls. MSCs were identified by their immunophenotypic characteristics and their potential to differentiate towards adipocytes/osteocytes/chondrocytes. We evaluated the mRNA expression of genes involved in the lung injury of IPF, namely the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor beta-1 (TGF-beta1) and the axis stromal-cell-derived factor-1 (SDF-1)/CXCR4 in BM MSCs using quantitative RT-PCR.


RESULTS
The BM MSCs of IPF patients displayed normal immunophenotypic characteristics and differentiation potential. No statistically significant difference was found between patients and controls in VEGF and FGF mRNA expression. TGF-beta1 was not expressed in either patients or controls. A significant increase in SDF-1-TR1 and CXCR4 mRNA expression was detected in IPF patients (1.6 x 10(25) +/- 1.2 x 10(25) and 3.1 x 10(7) +/- 3.1 x 10(7), respectively) compared to controls (0.32 x 10(25) +/- 0.07 x 10(25) and 1.67 x 10(7) +/- 0.30 x 10(7), respectively) (p = 0.001 and p = 0.001, respectively) whereas SDF-1 levels in MSC supernatants were similar in patients and controls.


CONCLUSIONS
The increased CXCR4 expression by patient MSCs suggests that the BM is probably implicated in the pathophysiology of IPF by mobilizing MSCs in response to or preceding lung injury. The potential role of BM MSCs in IPF is another interesting field for further investigation.
Antoniou
Katerina M
KM
Department of Thoracic Medicine, Interstitial Lung Disease Unit, Medical School, University of Crete, Heraklion Crete, Greece. katerinaantoniou@yahoo.gr
Papadaki
Helen A
HA
Soufla
Giannoula
G
Kastrinaki
Maria Christina
MC
Damianaki
Athina
A
Koutala
Helen
H
Spandidos
Demetrios A
DA
Siafakas
Nikolaos M
NM
D000328:Adult; D000368:Aged; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors