Glioblastoma therapy with cytotoxic mesenchymal stromal cells optimized by bioluminescence imaging of tumor and therapeutic cell response
Alieva, Maria (Centro de Investigación Biomédica en Red)
Bagó, Juli R. (Centro de Investigación Biomédica en Red)
Aguilar, Elisabet (Centro de Investigación Biomédica en Red)
Soler-Botija, Carolina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Vila, Olaia F. (Centro de Investigación Biomédica en Red)
Molet, Joan (Institut d'Investigació Biomèdica Sant Pau)
Gambhir, Sanjiv S. (Stanford University)
Rubio, Nuria (Centro de Investigación Biomédica en Red)
Blanco, Jerónimo (Centro de Investigación Biomédica en Red)
Universitat Autònoma de Barcelona

Date:	2012
Abstract:	Genetically modified adipose tissue derived mesenchymal stromal cells (hAMSCs) with tumor homing capacity have been proposed for localized therapy of chemo- and radiotherapy resistant glioblastomas. We demonstrate an effective procedure to optimize glioblastoma therapy based on the use of genetically modified hAMSCs and in vivo non invasive monitoring of tumor and therapeutic cells. Glioblastoma U87 cells expressing Photinus pyralis luciferase (Pluc) were implanted in combination with hAMSCs expressing a trifunctional Renilla reniformis luciferase-red fluorescent protein-thymidine kinase reporter in the brains of SCID mice that were subsequently treated with ganciclovir (GCV). The resulting optimized therapy was effective and monitoring of tumor cells by bioluminescence imaging (BLI) showed that after 49 days GCV treatment reduced significantly the hAMSC treated tumors; by a factor of 10 relative to controls. Using a Pluc reporter regulated by an endothelial specific promoter and in vivo BLI to image hAMSC differentiation we gained insight on the therapeutic mechanism. Implanted hAMSCs homed to tumor vessels, where they differentiated to endothelial cells. We propose that the tumor killing efficiency of genetically modified hAMSCs results from their association with the tumor vascular system and should be useful vehicles to deliver localized therapy to glioblastoma surgical borders following tumor resection. © 2012 Alieva et al.
Grants:	Ministerio de Ciencia e Innovación SAF2009-07102 Ministerio de Ciencia e Innovación SAF2009-07315E
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 7 Núm. 4 (17 2012) , p. e35148, ISSN 1932-6203

DOI: 10.1371/journal.pone.0035148
PMID: 22529983

11 p, 664.3 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles