title: Impairment in immunomodulatory function of mesenchymal stem cells from multiple myeloma patients.
abstract: OBJECTIVE
  Abnormality of immune regulation exists in multiple myeloma (MM). Mesenchymal stem cells (MSCs), a key regulator for immunomodulatory function, have decreased osteogenic potential in MM patients. Here we investigated the immunomodulatory function of MSCs from MM patients (MM-MSCs) and its relationship with decreased osteogenic potential.
  
  
  METHODS
  Real-time PCR was performed to detect the cytokines expressed in MM-MSCs (n = 22) and MSCs from normal donors (ND-MSCs, n = 11). Lymphocyte proliferative assay was used to detect the effect of MSCs on T cell proliferation. The effect of MSCs on T-cell cycle and T-cell activation markers expression were analyzed by flow cytometry. Flow cytometry and Western blot were used to detect apoptosis of T cells. Influence of T cells on osteogenic potential of MSCs was detected.
  
  
  RESULTS
  MM-MSCs exhibited increased expression of TGF-β1, IL-6, IL-3, TNF-α and RANKL and decreased expression of TGF-β2, TGF-β3 and FasL. The inhibitory effect of MM-MSCs on T.cell proliferative ability was attenuated. ND-MSCs silence more T cells in G0/G1 phase than MM-MSCs. The apoptosis-promoting effect of MM-MSCs on T cells seemed to be dampened. Expression of T-cell activation markers was significantly inhibited by ND-MSCs. T cells from normal donors possessed the ability to promote osteoblastic differentiation of ND-MSCs, but this ability of T cells both directly from MM patients and co-cultured with MM-MSCs was impaired.
  
  
  CONCLUSIONS
  MSCs from MM patients showed impaired immunoinhibitory capability on T cells, which in turn lose the ability to stimulate osteogenesis of MSCs.
authors.affiliation: Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
authors.forename: Bingzong
authors.initials: B
authors.lastname: Li
authors.forename: Jinxing
authors.initials: J
authors.lastname: Fu
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Wenzhuo
authors.initials: W
authors.lastname: Zhuang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D008213:Lymphocyte Activation; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology* / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D007155:Immunologic Factors