title: Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) have been promoted as an attractive option to use as cellular delivery vehicles to carry anti-tumor agents, owing to their ability to home into tumor sites and secrete cytokines. Multiple isolated populations have been described as MSCs, but despite extensive in vitro characterization, little is known about their in vivo behavior.The aim of this study was to investigate the efficacy and efficiency of different MSC lineages derived from five different sources (bone marrow, adipose tissue, epithelial endometrium, stroma endometrium, and amniotic membrane), in order to assess their adequacy for cell-based anti-tumor therapies. Our study shows the crucial importance of understanding the interaction between MSCs and tumor cells, and provides both information and a methodological approach, which could be used to develop safer and more accurate targeted therapeutic applications.
  
  
  METHODS
  We first measured the in vivo migration capacity and effect on tumor growth of the different MSCs using two imaging techniques: (i) single-photon emission computed tomography combined with computed tomography (SPECT-CT), using the human sodium iodine symporter gene (hNIS) and (ii) magnetic resonance imaging using superparamagnetic iron oxide. We then sought correlations between these parameters and expression of pluripotency-related or migration-related genes.
  
  
  RESULTS
  Our results show that migration of human bone marrow-derived MSCs was significantly reduced and slower than that obtained with the other MSCs assayed and also with human induced pluripotent stem cells (hiPSCs). The qPCR data clearly show that MSCs and hiPSCs exert a very different pluripotency pattern, which correlates with the differences observed in their engraftment capacity and with their effects on tumor growth.
  
  
  CONCLUSIONS
  This study reveals differences in MSC recruitment/migration toward the tumor site and the corresponding effects on tumor growth. Three observations stand out: 1) tracking of the stem cell is essential to check the safety and efficacy of cell therapies; 2) the MSC lineage to be used in the cell therapy needs to be carefully chosen to balance efficacy and safety for a particular tumor type; and 3) different pluripotency and mobility patterns can be linked to the engraftment capacity of the MSCs, and should be checked as part of the clinical characterization of the lineage.
authors.affiliation: Instituto Aragones de Ciencias de la Salud-IIS Aragon, Zaragoza, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Belmar-Lopez
authors.forename: Gracia
authors.initials: G
authors.lastname: Mendoza
authors.forename: Daniel
authors.initials: D
authors.lastname: Oberg
authors.forename: Jerome
authors.initials: J
authors.lastname: Burnet
authors.forename: Carlos
authors.initials: C
authors.lastname: Simon
authors.forename: Irene
authors.initials: I
authors.lastname: Cervello
authors.forename: Maite
authors.initials: M
authors.lastname: Iglesias
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ramirez
authors.forename: Pilar
authors.initials: P
authors.lastname: Lopez-Larrubia
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintanilla
authors.forename: Pilar
authors.initials: P
authors.lastname: Martin-Duque
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D006367:HeLa Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000000981:diagnostic imaging* / Q000502:physiology; D008279:Magnetic Resonance Imaging / Q000379:methods; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000000981:diagnostic imaging* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000601:surgery; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods