Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats
Natalia Yudintceva,
Ekaterina Lomert,
Natalia Mikhailova,
Elena Tolkunova,
Nikol Agadzhanian,
Konstantin Samochernych,
Gabriele Multhoff,
Grigoriy Timin,
Vyacheslav Ryzhov,
Vladimir Deriglazov,
Anton Mazur,
Maxim Shevtsov
Affiliations
Natalia Yudintceva
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Ekaterina Lomert
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Natalia Mikhailova
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Elena Tolkunova
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Nikol Agadzhanian
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Konstantin Samochernych
Personalized Medicine Centre, Almazov National Medical Research Centre, Polenov Russian Scientific, Research Institute of Neurosurgery, 197341 St. Petersburg, Russia
Gabriele Multhoff
Central Institute for Translational Cancer Research (TranslaTUM), Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University of Munich, 81675 Munich, Germany
Grigoriy Timin
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Vyacheslav Ryzhov
Petersburg Nuclear Physics Institute Named by B.P.Konstantinov of National Research Center “Kurchatov Institute”, 188300 Gatchina, Russia
Vladimir Deriglazov
Petersburg Nuclear Physics Institute Named by B.P.Konstantinov of National Research Center “Kurchatov Institute”, 188300 Gatchina, Russia
Anton Mazur
Magnetic Resonance Research Center, Saint-Petersburg State University, 199034 St. Petersburg, Russia
Maxim Shevtsov
Institute of Cytology of the Russian Academy of Sciences (RAS), 194064 St. Petersburg, Russia
Despite multimodal approaches for the treatment of multiforme glioblastoma (GBM) advances in outcome have been very modest indicating the necessity of novel diagnostic and therapeutic strategies. Currently, mesenchymal stem cells (MSCs) represent a promising platform for cell-based cancer therapies because of their tumor-tropism, low immunogenicity, easy accessibility, isolation procedure, and culturing. In the present study, we assessed the tumor-tropism and biodistribution of the superparamagnetic iron oxide nanoparticle (SPION)-labeled MSCs in the orthotopic model of C6 glioblastoma in Wistar rats. As shown in in vitro studies employing confocal microscopy, high-content quantitative image cytometer, and xCelligence system MSCs exhibit a high migratory capacity towards C6 glioblastoma cells. Intravenous administration of SPION-labeled MSCs in vivo resulted in intratumoral accumulation of the tagged cells in the tumor tissues that in turn significantly enhanced the contrast of the tumor when high-field magnetic resonance imaging was performed. Subsequent biodistribution studies employing highly sensitive nonlinear magnetic response measurements (NLR-M2) supported by histological analysis confirm the retention of MSCs in the glioblastoma. In conclusion, MSCs due to their tumor-tropism could be employed as a drug-delivery platform for future theranostic approaches.
