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Open Access Research article

Tissue-derived mesenchymal stromal cells used as vehicles for anti-tumor therapy exert different in vivo effects on migration capacity and tumor growth

Carolina Belmar-Lopez1, Gracia Mendoza1, Daniel Oberg2, Jerome Burnet3, Carlos Simon4, Irene Cervello4, Maite Iglesias5, Juan Carlos Ramirez6, Pilar Lopez-Larrubia7, Miguel Quintanilla7 and Pilar Martin-Duque158*

Author Affiliations

1 Instituto Aragones de Ciencias de la Salud-IIS Aragon, Zaragoza, Spain

2 Department of Medical Biochemistry and Microbiology, The Biomedical Centre, Uppsala University, Uppsala, Sweden

3 Queen Mary, University of London/Cancer Research UK, London, UK

4 Fundacion IVI, Instituto Universitario IVI, University of Valencia, Institute of Health Research INCLIVA, Valencia, Spain

5 Facultad de Ciencias Biosanitarias, Universidad Francisco de Vitoria, Madrid, Spain

6 Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain

7 Instituto de Investigaciones Biomedicas Alberto Sols (CSIC-UAM), Madrid, Spain

8 Fundacion Araid, Zaragoza, Spain

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BMC Medicine 2013, 11:139  doi:10.1186/1741-7015-11-139

Published: 28 May 2013

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.

Conclusion

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.

Keywords:
Mesenchymal stromal cells; Migration; In vivo imaging; Tumor growth; Pluripotency