title: Evidences of early senescence in multiple myeloma bone marrow mesenchymal stromal cells.
abstract: BACKGROUND
  In multiple myeloma, bone marrow mesenchymal stromal cells support myeloma cell growth. Previous studies have suggested that direct and indirect interactions between malignant cells and bone marrow mesenchymal stromal cells result in constitutive abnormalities in the bone marrow mesenchymal stromal cells.
  
  
  METHODS
  The aims of this study were to investigate the constitutive abnormalities in myeloma bone marrow mesenchymal stromal cells and to evaluate the impact of new treatments.
  
  
  RESULTS
  We demonstrated that myeloma bone marrow mesenchymal stromal cells have an increased expression of senescence-associated β-galactosidase, increased cell size, reduced proliferation capacity and characteristic expression of senescence-associated secretory profile members. We also observed a reduction in osteoblastogenic capacity and immunomodulatory activity and an increase in hematopoietic support capacity. Finally, we determined that current treatments were able to partially reduce some abnormalities in secreted factors, proliferation and osteoblastogenesis.
  
  
  CONCLUSIONS
  We showed that myeloma bone marrow mesenchymal stromal cells have an early senescent profile with profound alterations in their characteristics. This senescent state most likely participates in disease progression and relapse by altering the tumor microenvironment.
authors.affiliation: Laboratory of Clinical Cell Therapy, Université Libre de Bruxelles (ULB), Institut Jules Bordet, Brussels, Belgium. thibaud.andre@bordet.be
authors.forename: Thibaud
authors.initials: T
authors.lastname: André
authors.forename: Nathalie
authors.initials: N
authors.lastname: Meuleman
authors.forename: Basile
authors.initials: B
authors.lastname: Stamatopoulos
authors.forename: Cécile
authors.initials: C
authors.lastname: De Bruyn
authors.forename: Karlien
authors.initials: K
authors.lastname: Pieters
authors.forename: Dominique
authors.initials: D
authors.lastname: Bron
authors.forename: Laurence
authors.initials: L
authors.lastname: Lagneaux
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016922:Cellular Senescence; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006410:Hematopoiesis; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000166:cytology; D012008:Recurrence; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D001616:beta-Galactosidase
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