title: Intrinsic growth deficiencies of mesenchymal stromal cells in myelodysplastic syndromes.
abstract: Myelodysplastic syndromes (MDSs) are clonal disorders of hematopoietic stem cells (HSCs) characterized by ineffective hematopoiesis. MDSs are responsible for 1 or several peripheral cytopenias. The evidence accumulated in recent years demonstrates that in addition to HSC defects, a particular role is also played by stromal microenvironment dysfunctions, which mediate the direct contact with hematopoietic precursor cells (HPCs). These interactions help regulate different adhesion-related processes, such as progenitor cell proliferation, apoptosis, clonogenic growth, and maintenance in in vitro cultures. As previously reported, these interactions are responsible for altering the microenvironment in MDS. Herein, we present a novel selection protocol for obtaining a standards-compliant mesenchymal stromal cell (MSC) preparation. This method allowed us to comparatively analyze 2 subpopulations of bone marrow MSCs (BM-MSCs) in terms of their adhesion profiles and growth abilities: BM-MSCs selected from MDS settings and their normal counterparts. Functional assays revealed that the MSCs from MDS are intrinsically pathological, thus showing a continuous decline of proliferation and a reduced clonogenic capacity during 14 days of culture and in the absence of signals from hematopoietic cells. The MSC growth defects were significantly correlated with decreases in CD44 adhesion molecules and CD49e (α5-integrin).
authors.affiliation: Laboratoire d'Hématologie, Hôpital Nord, CHU de Saint-Etienne, Saint-Etienne Cedex, France. caanei@yahoo.com
authors.forename: Carmen Mariana
authors.initials: CM
authors.lastname: Aanei
authors.forename: Pascale
authors.initials: P
authors.lastname: Flandrin
authors.forename: Florin Zugun
authors.initials: FZ
authors.lastname: Eloae
authors.forename: Eugen
authors.initials: E
authors.lastname: Carasevici
authors.forename: Denis
authors.initials: D
authors.lastname: Guyotat
authors.forename: Eric
authors.initials: E
authors.lastname: Wattel
authors.forename: Lydia
authors.initials: L
authors.lastname: Campos
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000368:Aged; D000954:Antigens, Surface / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D016022:Case-Control Studies; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D048430:Cell Shape; D048429:Cell Size; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D016130:Immunophenotyping; D039482:Integrin alpha5 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*
chemical_list: D000954:Antigens, Surface; C497483:CD44 protein, human; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D018960:Hyaluronan Receptors; D039482:Integrin alpha5; C525591:STRO-1 antigen, human; D015720:5'-Nucleotidase; C548241:NT5E protein, human