title: [Immunomodulatory effects of mesenchymal stem cells derived from the bone marrow in acute leukemia patients].
abstract: OBJECTIVE
  To study the immunomodulatory effects and mechanisms of mesenchymal stem cells (MSC) derived from the bone marrow in acute leukemia patients in vitro.
  
  
  METHODS
  Bone marrow mononuclear cells from acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) were obtained and cultured in low serum medium. The immunophenotypes were assessed by FACS and immunol histochemistry. The levels of cytokines were evaluated by enzyme linked immunosorbant assay (ELISA). T-cell suppression ability was evaluated by Transwell chamber assay. Moreover, the immunoregulatory ability of AML- and ALL-derived MSC was detected by mixed lymphocyte culture assay.
  
  
  RESULTS
  ALL-derived MSC showed a typical fibroblast-like morphology. They were positive for CD29, CD44 and CD105, the positive rate were 98.81%, 99.25% and 90.52%, respectively, while negative for CD31, CD45 and CD34. Moreover, ALL- and AML-derived MSC didn't express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). ALL and AML derived MSC could secret several cytokines, such as TGF-β1 (567.58 ± 52.64 and 357.15 ± 33.52), HGF (647.27 ± 102.54 and 219.67 ± 62.37), IL-6 (59.67 ± 15.69 and 54.35 ± 12.31) and IL-11 (102.58 ± 23.54 and 78.21 ± 9.67), the level of secretion of TGF-β1 and HGF were higher in ALL bone marrow derived MSC than that of in AML bone marrow derived MSC. ALL and AML derived MSC significantly suppressed T lymphocyte proliferation in a dose-dependent manner, the counts per minute (CPM) were (3.58 ± 0.54) × 10(4), (2.87 ± 0.33) × 10(4), (1.78 ± 0.51) × 10(4) and (1.15 ± 0.15) × 10(4) for AML derived MSC, and CPM were (1.96 ± 0.31) × 10(4), (1.57 ± 0.28) × 10(4), (0.91 ± 0.41) × 10(4) and (0.22 ± 0.11) × 10(4) for ALL derived MSC when MSC were 0.5 × 10(4), 1 × 10(4), 2 × 10(4) and 5 × 10(4). In addition, the CPM was (4.01 ± 0.72) × 10(4) in control group. The immunosuppressive ability was different between MSCs derived from AML and ALL. The immunosuppressive effect of ALL derived MSC could be reversed by anti-TGF-β1 and anti-HGF antibody.
  
  
  CONCLUSIONS
  ALL-derived MSC show immunoregulatory effect in vitro and this effect is achieved through cytokines. But MSCs derived from AML display abnormal changes in T-cell suppression ability.
authors.affiliation: Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300020, China.
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Xiao-fang
authors.initials: XF
authors.lastname: Wang
authors.forename: Yi-zhuo
authors.initials: YZ
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Hong-liang
authors.initials: HL
authors.lastname: Yang
authors.forename: Ping
authors.initials: P
authors.lastname: Zou
mesh_terms: D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D016130:Immunophenotyping; D017370:Interleukin-11 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D059630:Mesenchymal Stem Cells; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016207:Cytokines; D017370:Interleukin-11; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1