Impairment in immuno-modulatory function of Flk1(+)CD31(-)CD34(-) MSCs from MDS-RA patients.
OBJECTIVE
Myelodysplastic syndromes are a group of hematopoietic disorders characterized by hematopoietic stem cell dysregulation and abnormalities in the immune system. Mesenchymal stem cells (MSCs) and their derived stromal cells constitute a bone marrow microenvironment, which is the niche for hematopoiesis and a key compartment for immune development and regulation. Existing evidence has shown that MSCs from MDS patients have impaired capacity in supporting hematopoiesis. Here, we conducted an investigation to determine whether the immuno-modulatory function of MSCs is also impaired in MDS-RA (refractory anemia) patients.


METHODS
Flk1(+)CD31(-)CD34(-) MSCs were isolated from 15 MDS-RA patients and cultured for testing biological and immunological characteristics.


RESULTS
MDS-RA patient-derived Flk1(+)CD31(-)CD34(-) MSCs showed normal morphology, phenotype and karyotype but appeared impaired in immuno-modulatory function. The capacity of patient Flk1(+)CD31(-)CD34(-) MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. In conclusion, MDS-RA patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than HSCs. MSCs might be a potential target for developing efficacious cures for MDS.
Han
Qin
Q
Institute of Basic Medical Sciences & School of Basic Medicine, Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Sun
Zhao
Z
Liu
Lihui
L
Chen
Bin
B
Cao
Ying
Y
Li
Kanghua
K
Zhao
Robert Chunhua
RC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology*; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D017931:DNA Primers; D005260:Female; D006801:Humans; D007621:Karyotyping; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
D018952:Antigens, CD34; D017931:DNA Primers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2