Matrix metalloproteinase-9 was involved in the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukemia patients  

作　　者：ZHU Xi-shan SHI Wei AN Guang-yu ZHANG Hong-mei SONG Yu-guang LI You-bin 

机构地区：[1]Institute of Internal Oncology, Center of Tumor Research andTherapy, Beijing Shijitan Hospital, Capital Medical University (theNinth Medical College of Peking University), Beijing 100038,China

出　　处：《Chinese Medical Journal》2011年第16期2423-2430,共8页中华医学杂志（英文版）

摘　　要：Background Overwhelming 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. Methods We have previously isolated fetal liver kinase-l-positive （Flkl＋） 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 FIk1＋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. Results CML patient-derived FIk1＋CD31-CD34- MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient FIk1＋CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. Conclusions CML 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.Background Overwhelming 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. Methods We have previously isolated fetal liver kinase-l-positive （Flkl＋） 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 FIk1＋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. Results CML patient-derived FIk1＋CD31-CD34- MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient FIk1＋CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. Conclusions CML 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.

关 键 词：chronic myeloid leukemia mesenchymal stem cell immune regulation matrix metalloproteinase-9 

分 类 号：Q511[生物学—生物化学] TS218[轻工技术与工程—粮食、油脂及植物蛋白工程]