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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
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Καραγιάννης, Κωνσταντίνος
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Thesis advisor
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Τζανάκης, Νικόλαος
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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.
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Language |
Greek |
Subject |
COPD |
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Chemokines |
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Migration |
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Real-time PCR |
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Αρχέγονα μεσεγχυματικά κύτταρα |
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Μεταναστευτικότητα |
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ΧΑΠ |
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Χημειοκίνες |
Issue date |
2022-07-29 |
Collection
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School/Department--School of Medicine--Department of Medicine--Doctoral theses
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Type of Work--Doctoral theses
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Permanent Link |
https://elocus.lib.uoc.gr//dlib/c/9/5/metadata-dlib-1657192924-512989-676.tkl
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Views |
285 |
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