925 Neoplasma 63, 6, 2016 doi:10.4149/neo_2016_611 Dental pulp mesenchymal stem/stromal cells labeled with iron sucrose release exosomes and cells applied intra-nasally migrate to intracerebral glioblastoma U. ALTANEROVA 1 , K. BENEJOVA 1 , V. ALTANEROVA 1,2 , S. TYCIAKOVA 2 , B. RYCHLY 3 , P. SZOMOLANYI 4 , F. CIAMPOR 5 , M. CIHOVA 2 , V. REPISKA 6 , K. ONDICOVA 7 , B. MRAVEC 7 , C. ALTANER 1,2, * 1 St. Elisabeth Cancer Institute, Centre for Cell erapy and Regenerative Medicine, Bratislava, Slovakia; 2 Cancer Research Institute, Biomedi- cal Center, Slovak Academy of Sciences, Bratislava, Slovakia; 3 Cytopathos, Ltd., Bratislava, Slovakia; 4 Department of Biomedical Imaging and Image-guided erapy, Medical University of Vienna, Austria; 5 Institute of Virology, Biomedical Center, Slovak Academy of Sciences, Bratislava, Slovakia; 6 Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University in Bratislava, Slovakia; 7 Institute of Pathophysiology, Faculty of Medicine, Comenius University in Bratislava, Slovakia *Correspondence: exonalt@savba.sk Received May 2, 2016 / Accepted June 9, 2016 We report on a simple iron oxide (Venofer) labeling procedure of dental pulp mesenchymal stem cells (DP-MSCs) and DP- MSCs transduced with yeast cytosinedeaminase::uracilphosphoribosyltransferase (yCD::UPRT-DP-MSCs). Venofer is a drug approved for intravenous application to treat iron deficiency anemia in patients. Venofer labeling did not affect DP-MSCs or yCD::UPRT-DP-MSCs viability and growth kinetics. Electron microscopy of labeled cells showed internalized Venofer nano- particles in endosomes. MRI relativity measurement of Venofer labeled DP-MSCs in a phantom arrangement revealed that 100 cells per 0.1 ml were still detectable. DP-MSCs or yCD::UPRT-DP-MSCs and the corresponding Venofer labeled cells release exosomes into conditional medium (CM). CM from yCD::UPRT-DP-MSCs in the presence of a prodrug 5-fluorocytosine caused tumor cell death in a dose dependent manner. Iron labeled DP-MSCs or yCD::UPRT-DP-MSCs sustained their tumor tropism in vivo; intra-nasally applied cells migrated and specifically engraſted orthotopic glioblastoma xenograſts in rats. Key words: dental pulp MSCs, iron labeling, yCD::UPRT-exosomes, intranasal application, migration to intracerebral glioblastoma Mesenchymal (stromal) stem cells (MSCs) can be readily iso- lated from human tissues like bone marrow, adipose, umbilical cord, dental pulp and others. MSCs represent novel promising therapeutic tools of emerging regenerative medicine. MSCs of different origin are tested in large number of clinical trials for treatment of diseases, which do not have at present adequate therapy. As of July 2016, the public clinical trials database showed 627 clinical trials using MSCs for a very wide range of therapeutic applications [1]. It has been increasingly observed that the transplanted MSCs did not necessarily engraſt and dif- ferentiate at the site of injury but might exert their therapeutic effects through paracrine manner inducing endogenous repara- tory processes. It has been recognized that MSCs released rich secretome together with extracellular exosomes that might be responsible at least to some degree for transfer of regulatory gene products needed for reparatory processes induction [2]. e therapeutic potential of MSCs-derived extracellular vesicles was recently comprehensively reviewed [3]. Dental pulp derived mesenchymal stem cells (DP-MSCs) are known for the high proliferative potential for self-renewal, plasticity and multipotential capabilities. Dental pulp is made of ecto-mesenchymal elements, containing neural crest- derived cells. DP-MSCs are intensively studied because of their neural characteristics being considered as cells for the periph- eral neural regeneration [4]. Our comparison of DP-MSCs with bone marrow and adipose tissues derived MSCs revealed differences in the expression of pluripotent stem cells genes that reflected ecto-mesenchymal origin of DP-MSCs [5]. MSCs engineered to express therapeutic gene products are becoming more promising in cancer therapy for their ability to selectively target tumor cells. eir administration in animal models resulted in successful inhibition of growth of variety