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Human adipose tissue-derived mesenchymal stromal cells as vehicles for tumor bystander effect: a model based on bioluminescence imaging

Gene Therapy volume 16, pages 547–557 (2009)Cite this article

Abstract

Human adipose tissue mesenchymal stromal cells (AMSCs) share common traits, including similar differentiation potential and cell surface markers, with their bone marrow counterparts. Owing to their general availability, higher abundance and ease of isolation AMSCs may be convenient autologous delivery vehicles for localized tumor therapy. We demonstrate a model for tumor therapy development based on the use of AMSCs expressing renilla luciferase and thymidine kinase, as cellular vehicles for ganciclovir-mediated bystander killing of firefly luciferase expressing tumors, and noninvasive bioluminescence imaging to continuously monitor both, tumor cells and AMSCs. We show that the therapy delivering AMSCs survive long time within tumors, optimize the ratio of AMSCs to tumor cells for therapy, and asses the therapeutic effect in real time. Treatment of mice bearing prostate tumors plus therapeutic AMSCs with the prodrug ganciclovir induced bystander killing effect, reducing the number of tumor cells to 1.5 % that of control tumors. Thus, AMSCs could be useful vehicles to deliver localized therapy, with potential for clinical application in inoperable tumors and surgical borders after tumor resection. This approach, useful to evaluate efficiency of therapeutic models, should facilitate the selection of cell types, dosages, therapeutic agents and treatment protocols for cell-based therapies of specific tumors.

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Acknowledgements

This study was funded in part by grants from Fundació Marató TV3 (Ref no. 050210), Fondo de Investigación Sanitaria (FIS, PI 060208), Ministerio de Educación y Ciencia (SAF 2007-62472), Red Temática de Investigación Cooperativa TERCEL.

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Authors and Affiliations

  1. Cardiovascular Research Center (CSIC-ICCC), CIBER-BBN, Barcelona, Spain

    M Vilalta, I R Dégano, J Bagó, E Aguilar, N Rubio & J Blanco

  2. Department of Radiology, The Bio-X Program, Stanford University, Palo Alto, CA, USA

    S S Gambhir

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  1. M Vilalta
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  2. I R Dégano
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  7. J Blanco
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Correspondence to J Blanco.

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Supplementary Information accompanies the paper on Gene Therapy website (http://www.nature.com/gt)

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Vilalta, M., Dégano, I., Bagó, J. et al. Human adipose tissue-derived mesenchymal stromal cells as vehicles for tumor bystander effect: a model based on bioluminescence imaging. Gene Ther 16, 547–557 (2009). https://doi.org/10.1038/gt.2008.176

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