Dental pulp mesenchymal stem/stromal cells labeled with iron sucrose release exosomes and cells applied intra-nasally migrate to intracerebral glioblastoma

被引:40
作者
Altanerova, U. [1 ]
Benejova, K. [1 ]
Altanerova, V. [1 ,2 ]
Tyciakova, S. [2 ]
Rychly, B. [3 ]
Szomolanyi, P. [4 ]
Ciampor, F. [5 ]
Cihova, M. [2 ]
Repiska, V. [6 ]
Ondicova, K. [7 ]
Mravec, B. [7 ]
Altaner, C. [1 ,2 ]
机构
[1] Ctr Cell Therapy & Regenerat Med, St Elisabeth Canc Inst, Bratislava, Slovakia
[2] Slovak Acad Sci, Biomed Ctr, Canc Res Inst, Bratislava, Slovakia
[3] Cytopathos Ltd, Bratislava, Slovakia
[4] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria
[5] Slovak Acad Sci, Biomed Ctr, Inst Virol, Bratislava, Slovakia
[6] Comenius Univ, Fac Med, Inst Med Biol Genet & Clin Genet, Bratislava, Slovakia
[7] Comenius Univ, Fac Med, Inst Pathophysiol, Bratislava, Slovakia
关键词
dental pulp MSCs; iron labeling; yCD::UPRT-exosomes; intranasal application; migration to intracerebral glioblastoma; CANCER GENE-THERAPY; STEM-CELLS; ADIPOSE-TISSUE; BONE-MARROW; CAPABILITY; DELIVERY;
D O I
10.4149/neo_2016_611
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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 engrafted orthotopic glioblastoma xenografts in rats.
引用
收藏
页码:925 / 933
页数:9
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