|
|
| Identifier |
000399243 |
| Title |
Διερεύνηση των παθογενετικών μηχανισμών που διέπουν τις ποιοτικές ανωμαλίες των μυελικών μεσεγχυματικών προγονικών κυττάρων σε πάσχοντες από μυελοδυσπλαστικά σύνδρομα |
| Alternative Title |
Investigation of the pathogenetic mechanisms underlying the functional abnormalities of mesenchymal stem cells in patients with myelodysplastic syndromes |
|
Author
|
Παυλάκη, Κωνσταντία
|
|
Thesis advisor
|
Παπαδάκη, Ελένη
|
|
Reviewer
|
Γουλιέλμος, Γιώργος
Παπαματθαιάκη, Σήφη
|
| Abstract |
It has been shown that bone marrow mesenchymal stem cells (MSCs) from
patients with myelodysplastic syndromes (MDS) display defective proliferative
potential. We have probed the impaired replicative capacity of culture
expanded MSCs in MDS patients (n=30) compared with healthy subjects
(n=32) by studying senescence characteristics and gene expression
associated with WNT/transforming growth factor-β1 (TGFB1) signaling
pathways. We have also explored the consequences of the impaired patient
MSC proliferative potential by investigating their differentiation potential and
the capacity to support normal CD34+ cell growth under coculture conditions.
Patient MSCs displayed decreased gene expression of the senescenceassociated
cyclin-dependent kinase inhibitors CDKN1A (p21), CDKN2A (p16),
and CDKN2B (p15), along with PARG1, whereas their mean telomere length
was upregulated. MDS-derived MSCs exhibited impaired capacity to support
normal CD34+ myeloid and erythroid colony formation. No significant changes
were observed between patients and controls in gene expression related to
TGFB1 pathway. Patient MSCs displayed upregulated noncanonical WNT
expression, downregulated canonical WNT expression and upregulate
canonical WNT inhibitors. MDS-derived MSCs displayed defective osteogenic
and adipogenic lineage priming under non-differentiating culture conditions.
Pharmacological activation of canonical WNT signaling in patient MSCs led to
an increase in cell proliferation and upregulation in the expression of early
osteogenesis-related genes. This study indicates abnormal WNT signaling in
MSCs of MDS patients and supports the concept of a primary MSC defect that
might have a contributory effect in MDS natural history.
|
| Language |
Greek |
| Subject |
MDS |
|
WNT |
| Issue date |
2016-03-24 |
| Collection
|
School/Department--School of Medicine--Department of Medicine--Doctoral theses
|
|
|
Type of Work--Doctoral theses
|
| Views |
298 |
Διερεύνηση των παθογενετικών μηχανισμών που διέπουν τις ποιοτικές ανωμαλίες των μυελικών μεσεγχυματικών προγονικών κυττάρων σε πάσχοντες από μυελοδυσπλαστικά σύνδρομα
