title: Study of the quantitative, functional, cytogenetic, and immunoregulatory properties of bone marrow mesenchymal stem cells in patients with B-cell chronic lymphocytic leukemia.
abstract: The bone marrow (BM) microenvironment has clearly been implicated in the pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL). However, the potential involvement of BM stromal progenitors, the mesenchymal stem cells (MSCs), in the pathophysiology of the disease has not been extensively investigated. We expanded in vitro BM-MSCs from B-CLL patients (n=11) and healthy individuals (n=16) and comparatively assessed their reserves, proliferative potential, differentiation capacity, and immunoregulatory effects on T- and B-cells. We also evaluated the anti-apoptotic effect of patient-derived MSCs on leukemic cells and studied their cytogenetic characteristics in comparison to BM hematopoietic cells. B-CLL-derived BM MSCs exhibit a similar phenotype, differentiation potential, and ability to suppress T-cell proliferative responses as compared with MSCs from normal controls. Furthermore, they do not carry the cytogenetic abnormalities of the leukemic clone, and they exert a similar anti-apoptotic effect on leukemic cells and healthy donor-derived B-cells, as their normal counterparts. On the other hand, MSCs from B-CLL patients significantly promote normal B-cell proliferation and IgG production, in contrast to healthy-donor-derived MSCs. Furthermore, they have impaired reserves, defective cellular growth due to increased apoptotic cell death and exhibit aberrant production of stromal cell-derived factor 1, B-cell activating factor, a proliferation inducing ligand, and transforming growth factor β1, cytokines that are crucial for the survival/nourishing of the leukemic cells. We conclude that ex vivo expanded B-CLL-derived MSCs harbor intrinsic qualitative and quantitative abnormalities that may be implicated in disease development and/or progression.
authors.affiliation: Department of Hematology, University of Crete School of Medicine, Heraklion, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Pontikoglou
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Kastrinaki
authors.forename: Mirjam
authors.initials: M
authors.lastname: Klaus
authors.forename: Christina
authors.initials: C
authors.lastname: Kalpadakis
authors.forename: Pavlos
authors.initials: P
authors.lastname: Katonis
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Alpantaki
authors.forename: Gerassimos A
authors.initials: GA
authors.lastname: Pangalis
authors.forename: Helen A
authors.initials: HA
authors.lastname: Papadaki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology; D016022:Case-Control Studies; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G