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Identifier

000449641

Title

Ο ρόλος των πρόδρομων μεσεγχυματικών κυττάρων μυελού των οστών στη Χρόνια Αποφρακτική Πνευμονοπάθεια

Alternative Title

The role of bone marow derived mesenchymal stem cells in chronic obstructive

Author

Καραγιάννης, Κωνσταντίνος

Thesis advisor

Τζανάκης, Νικόλαος

Abstract

Introduction Defective tissue repair and remodeling are main aspects of Chronic Obstructive Pulmonary Disease (COPD) pathophysiology. Bone marrow mesenchymal stem cells (BM-MSCs) have been implicated in this direction, as their functional impairment and recruitment could possibly contribute to disease development and progression. It is already known that chemokines, which are short positively charged peptides, are involved in BM-MSCs migration to areas of tissue injury. SDF- 1a/CXCR4 axis is the most studied chemokine ligand and receptor and a crucial role in lung tropism has been recently suggested. Additionally, it has showed that accelerated ageing, a common COPD pathogenetic mechanism, affects migratory capacity of BM-MSCs. The present study characterizes for the first time the expression of migration related chemokine receptors and their ligands in BM-MSCs from COPD patients. Methods Study population consists of twelve COPD patients and seven healthy subjects that visited lung function department of our hospital from June 2009 to February 2013. Ethical approval has been granted by research committee of the hospital and informed written consent was obtained from each participant. All the study participants had lung function tests, peripheral blood sample and bone marrow aspiration collected. MSCs isolation and culture from bone marrow aspirate was conducted until cell passage 2. Subsequently, RNA extraction was performed and culture conditioned media was stored. CXCR4/SDF-1a and CCR7/CCL19-CCL21 mRNA levels were evaluated in BMMSCs whereas SDF-1a protein levels in sera and BM-MSCs’ conditioned media were also evaluated. Results Demographic data showed no significant difference between COPD patients and healthy controls in view of age, gender, smoking history and body mass index. Lung Function Tests showed significant impairment in COPD group, as expected in comparison to control subjects. BM-MSCs were characterized based on their immunophenotypic propertied and their differentiation capacity, according to international minimal criteria for in vitro defining. CXCR4, SDF-1a, CCL19 and CCL21 mRNA levels were significantly reduced in COPD BM-MSCs while CCR7 levels were undetectable. Notably, SDF-1a protein levels were marginally elevated in both sera and ΒΜ-MSCs’ conditioned media while the increase in SDF-1a serum levels significantly correlated with disease severity in COPD. Conclusion Our findings show significant downregulation of SDF-1a and CXCR4 mRNA in BM-MSCs of COPD patients, indicating an involvement of the axis in the disease pathophysiology.

Language

Greek

Subject

COPD

Chemokines

Migration

Real-time PCR

Αρχέγονα μεσεγχυματικά κύτταρα

Μεταναστευτικότητα

ΧΑΠ

Χημειοκίνες

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