title: Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.
abstract: BACKGROUND
  Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL), significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM) mesenchymal stem cells (MSC) on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL.
  
  
  RESULTS
  The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(-) Burkitt-type BJAB, median survival = 46 days) and an aggressive (EBV(+) B lymphoblastoid SKW6.4, median survival = 27 days) behavior in nude-SCID mice. Intra-peritoneal (i.p.) injection of MSC (4 days after i.p. injection of lymphoma cells) significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days). Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i) MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii) MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures.
  
  
  CONCLUSIONS
  Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.
authors.affiliation: Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Secchiero
authors.forename: Sonia
authors.initials: S
authors.lastname: Zorzet
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Federica
authors.initials: F
authors.lastname: Corallini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Melloni
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Caruso
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bosco
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ingrao
authors.forename: Barbara
authors.initials: B
authors.lastname: Zavan
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D014183:Transplantation, Heterologous