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Blood, 15 January 2007, Vol. 109, No. 2, pp. 693-702.
Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2006-05-020800.
Previous Article | Next Article 
Submitted May 2, 2006
Accepted August 29, 2006
Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: Role of stromal cells in follicular lymphoma pathogenesis
Patricia Ame-Thomas, Helene Maby-El Hajjami, Celine Monvoisin, Rachel Jean, Delphine Monnier, Sylvie Caulet-Maugendre, Thierry Guillaudeux, Thierry Lamy, Thierry Fest, and Karin Tarte*
Faculte de Medecine, University Rennes, Rennes, France
UF SITI, Departement HITC, CHU Pontchaillou, Rennes, France
Laboratoire d'Anatomie Pathologique, CHU Pontchaillou, Rennes, France
Service d'Hematologie Clinique, CHU Pontchaillou, Rennes, France
* Corresponding author; email: karin.tarte{at}univ-rennes1.fr.
There is accumulating evidence that cellular microenvironment plays a key role in follicular lymphoma (FL) pathogenesis, both within tumor lymph nodes and in infiltrated bone marrow where ectopic lymph node-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 (FRC) mediate immune cell migration, adhesion, and reciprocal interactions. The role of FRC and their postulated progenitors, i.e. bone marrow mesenchymal stem cells (MSC), in FL remains unexplored. In this study, we have investigated the relationships between FRC and MSC and their capacity to sustain malignant B-cell growth. Our findings strongly suggest that secondary lymphoid organs contain MSC able to give rise to adipocytes, chondrocytes, osteoblasts, as well as fully functional B-cell supportive FRC. Bone marrow-derived MSC acquire in vitro a complete FRC phenotype in response to a combination of tumor necrosis factor- and lymphotoxin- 1 2. Moreover, MSC recruit primary FL cells that, in turn, trigger their differentiation into FRC, making them able to support malignant B-cell survival. Altogether, these new insights into the crosstalk between lymphoma cells and their microenvironment could offer original therapeutic strategies.

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