title: Cytotherapies in multiple myeloma: a complementary approach to current treatments?
abstract: BACKGROUND
  Based on their tumor tropism, mesenchymal stem cells (MSCs) have been proposed as carriers of cytotoxic molecules in pioneering strategies of anti-cancer gene therapy. Similar to solid tumors, MSCs, genetically modified to stably express the TNF-related apoptosis-inducing ligand (TRAIL), have been applied to counter-attack multiple myeloma (MM) in vitro and envisioned as a promising strategy for future anti-MM treatments.
  
  
  METHODS
  Accumulating evidence based on the detection of genetic and functional abnormalities in MSCs from MM patients points to the supportive function of MSCs in both the development and progression of MM, driven by chronic interplays with malignant cells within the marrow milieu. In this review, we revisit the function of MSCs in the pathophysiology of MM and explore the pivotal mechanisms of their interaction with myeloma cells. We also discuss the therapeutic significance of novel strategies using TRAIL-engineered MSCs in this cancer model, dissecting their role as new tools for future treatments against MM.
  
  
  CONCLUSIONS
  A cytotherapy based on TRAIL-engineered MSCs against MM may be successfully combined with either conventional approaches of autologous stem cell transplantation or with novel anti-MM drugs. Intensive preclinical investigations are required to identify the best sources as well as modalities of MSC administration, thus defining the translational suitability of this strategy in the clinical setting.
authors.affiliation: University of Bari A. Moro, Department of Biomedical Sciences and Human Oncology, Section of Clinical Oncology, Bari, Italy.
authors.forename: Sabino
authors.initials: S
authors.lastname: Ciavarella
authors.forename: Anna
authors.initials: A
authors.lastname: Caselli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Savonarola
authors.forename: Antonella Valentina
authors.initials: AV
authors.lastname: Tamma
authors.forename: Marco
authors.initials: M
authors.lastname: Tucci
authors.forename: Franco
authors.initials: F
authors.lastname: Silvestris
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D009101:Multiple Myeloma / Q000628:therapy*