title: Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis.
abstract: Accumulating evidence indicates that the cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes (LNs) and in infiltrated bone marrow where ectopic LN-like reticular cells are integrated within malignant B-cell nodular aggregates. In normal secondary lymphoid organs, specific stromal cell subsets provide a highly specialized microenvironment that supports immune response. In particular, fibroblastic reticular cells (FRCs) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRCs and their postulated progenitors, that is, bone marrow mesenchymal stem cells (MSCs), in FL remains unexplored. In this study, we investigated the relationships between FRCs and MSCs and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain MSCs able to give rise to adipocytes, chondrocytes, osteoblasts, as well as fully functional B-cell supportive FRCs. In vitro, bone marrow-derived MSCs acquire a complete FRC phenotype in response to a combination of tumor necrosis factor-alpha and lymphotoxin-alpha1beta2. Moreover, MSCs recruit primary FL cells that, in turn, trigger their differentiation into FRCs, making them able to support malignant B-cell survival. Altogether, these new insights into the cross talk between lymphoma cells and their microenvironment could offer original therapeutic strategies.
authors.affiliation: Unité Propre de Recherche de l'Enseignement Superieur Equipe d'Accueil 3889, Faculté de médicine, Université Rennes 1, and Département Hématologie-Immunologie et Thérapie Cellulaire, Centre Hospitalo-Universitaire Pontchaillou, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Amé-Thomas
authors.forename: Hélène
authors.initials: H
authors.lastname: Maby-El Hajjami
authors.forename: Céline
authors.initials: C
authors.lastname: Monvoisin
authors.forename: Rachel
authors.initials: R
authors.lastname: Jean
authors.forename: Delphine
authors.initials: D
authors.lastname: Monnier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Caulet-Maugendre
authors.forename: Thierry
authors.initials: T
authors.lastname: Guillaudeux
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.forename: Karin
authors.initials: K
authors.lastname: Tarte
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D006801:Humans; D008221:Lymphoid Tissue / Q000166:cytology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000276:immunology* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D014066:Palatine Tonsil / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology*