TY - THES
T1 - Characteristics of mesenchymal stromal cells from patients with myelodysplastic syndromes
AU - Liew, Lawrence
PY - 2012
Y1 - 2012
N2 - Myelodysplastic syndromes (MDS) constitute a group of haematological diseases which predominantly affects individuals over the age of 70. MDS is characterised by varying degree of ineffective haemopoiesis and early stages of MDS are often asymptomatic. The disease may progress to acute myeloid leukaemia (AML). The pathophysiology of MDS remains unresolved, however, recent studies have suggested that immune dysregulation in the bone marrow microenvironment and abnormalities of bone marrow mesenchymal stromal cells (MSC) may be involved in disease development. MSC are homogenous, multi-potent adult stem cells that constitute the bone marrow and play pivotal roles in supporting haemopoiesis and modulating the functions of immune cells. Morphological changes and functional aberrations in the bone marrow MSC compartment have been reported in haematological diseases including MDS and multiple myeloma. Whether the aberrations in MSC are sufficient to cause immune disturbance and the development of MDS is unclear. The current study aimed to characterise and compare bone marrow MSC from MDS patients with those of healthy individuals and to further examine the role of MSC in the pathogenesis of MDS. MSC were isolated from bone marrow aspirates of MDS patients (n=15) and characterised by growth kinetics, immunophenotype and tri-lineage differentiation potential. The production of pro-inflammatory cytokine IL-6 in culture was determined, as well as the immune modulatory functions of MSC. Cytogenetic analysis of MSC was performed, in comparison to bone marrow haemopoietic cells. The growth kinetics, immunophenotype and tri-lineage differentiation of MSC did not differ significantly between MDS patients and healthy individuals.
AB - Myelodysplastic syndromes (MDS) constitute a group of haematological diseases which predominantly affects individuals over the age of 70. MDS is characterised by varying degree of ineffective haemopoiesis and early stages of MDS are often asymptomatic. The disease may progress to acute myeloid leukaemia (AML). The pathophysiology of MDS remains unresolved, however, recent studies have suggested that immune dysregulation in the bone marrow microenvironment and abnormalities of bone marrow mesenchymal stromal cells (MSC) may be involved in disease development. MSC are homogenous, multi-potent adult stem cells that constitute the bone marrow and play pivotal roles in supporting haemopoiesis and modulating the functions of immune cells. Morphological changes and functional aberrations in the bone marrow MSC compartment have been reported in haematological diseases including MDS and multiple myeloma. Whether the aberrations in MSC are sufficient to cause immune disturbance and the development of MDS is unclear. The current study aimed to characterise and compare bone marrow MSC from MDS patients with those of healthy individuals and to further examine the role of MSC in the pathogenesis of MDS. MSC were isolated from bone marrow aspirates of MDS patients (n=15) and characterised by growth kinetics, immunophenotype and tri-lineage differentiation potential. The production of pro-inflammatory cytokine IL-6 in culture was determined, as well as the immune modulatory functions of MSC. Cytogenetic analysis of MSC was performed, in comparison to bone marrow haemopoietic cells. The growth kinetics, immunophenotype and tri-lineage differentiation of MSC did not differ significantly between MDS patients and healthy individuals.
KW - Myelodysplasia
KW - Immune dysregulation
KW - Mesenchymal stromal cells
KW - Cytokines
M3 - Master's Thesis
ER -