title: A peculiar molecular profile of umbilical cord-mesenchymal stromal cells drives their inhibitory effects on multiple myeloma cell growth and tumor progression.
abstract: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are under intensive investigation in preclinical models of cytotherapies against cancer, including multiple myeloma (MM). However, the therapeutic use of stromal progenitors holds critical safety concerns due to their potential MM-supporting activity in vivo. Here, we explored whether MSCs from sources other than BM, such as adipose tissue (AD-MSCs) and umbilical cord (UC-MSCs), affect MM cell growth in comparison to either normal (nBM-MSCs) or myelomatous marrow MSCs (MM-BM-MSCs). Results from both proliferation and clonogenic assays indicated that, in contrast to nBM- and MM-BM-MSCs, both AD and particularly UC-MSCs significantly inhibit MM cell clonogenicity and growth in vitro. Furthermore, when co-injected with UC-MSCs into mice, RPMI-8226 MM cells formed smaller subcutaneous tumor masses, while peritumoral injections of the same MSC subtype significantly delayed the tumor burden growing in subcutaneous plasmocytoma-bearing mice. Finally, both microarrays and ELISA revealed different expression of several genes and soluble factors in UC-MSCs as compared with other MSCs. Our data suggest that UC-MSCs have a distinct molecular profile that correlates with their intrinsic anti-MM activity and emphasize the UCs as ideal sources of MSCs for future cell-based therapies against MM.
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Ciavarella
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caselli
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Antonella Valentina
authors.initials: AV
authors.lastname: Tamma
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Savonarola
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Loverro
authors.affiliation: 2Department of Medicine and Sciences of Aging, Ce.S.I. Center for Aging Studies, Stem TECH Group, University "G. D'Annunzio," Chieti Scalo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Paganelli
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Tucci
authors.affiliation: 1Section of Medical Oncology, Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro," Bari, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000628:therapy*; D014470:Umbilical Cord / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*