Matrix metalloproteinase-9 was involved in the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukemia patients.
- Author:
Xi-Shan ZHU
1
;
Wei SHI
;
Guang-Yu AN
;
Hong-Mei ZHANG
;
Yu-Guang SONG
;
You-Bin LI
Author Information
- Publication Type:Journal Article
- MeSH: Adolescent; Adult; Antigens, CD34; genetics; metabolism; Apoptosis; drug effects; Blotting, Western; Cell Cycle; drug effects; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Fusion Proteins, bcr-abl; genetics; metabolism; Humans; Immunomodulation; In Situ Hybridization, Fluorescence; Karyotype; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; enzymology; immunology; metabolism; Male; Matrix Metalloproteinase 9; genetics; metabolism; Mesenchymal Stromal Cells; cytology; immunology; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; genetics; metabolism; T-Lymphocytes; Vascular Endothelial Growth Factor Receptor-2; genetics; metabolism; Young Adult
- From: Chinese Medical Journal 2011;124(16):2423-2430
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDOverwhelming evidences on chronic myeloid leukemia (CML) indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated.
METHODSWe have previously isolated fetal liver kinase-1-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of Ph(+) patients with hemangioblast property. In this study, we isolated CML patient-derived Flk1(+)CD31(-)CD34(-) mesenchymal stem cells (MSCs) and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization (FISH) analysis, fluorescence activated cell sorting (FACS), enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors.
RESULTSCML patient-derived Flk1(+)CD31(-)CD34(-) MSCs had normal morphology, phenotype and karyotype while 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.
CONCLUSIONSCML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells (HSCs). MSCs might be a potential target for developing efficacious treatment for CML.
