Abstract
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.
Highlights
Despite multimodal interdisciplinary treatment approaches [1,2], malignant gliomas, multiforme glioblastoma (GBM), are the most common types of brain tumors with very poor prognosis
Rat mesenchymal stem cells (MSCs) isolated from the rat aorta constituted a homogeneous population with a bipolar form (Figure 1A)
The incorporation of superparamagnetic iron oxide nanoparticle (SPION) with a dimension of less than 50 nm and a surface charge of −12.7 mV (Figure 1B) by cells at the ultrastructural level was analyzed by transmission electron microscopy (TEM)
Summary
Despite multimodal interdisciplinary treatment approaches [1,2], malignant gliomas, multiforme glioblastoma (GBM), are the most common types of brain tumors with very poor prognosis. Mesenchymal stem cells (MSCs) are an attractive solution for GBM therapy as they can augment the drug delivery across the BBB into the heterogenous glioma site [3]. Tumor tropism of stem cells of various origin (i.e., hematopoietic, embryonic, and, most widely used, mesenchymal) was further proven in the preclinical glioblastoma models [5]. Taking into consideration that currently MSCs (derived either from bone marrow or umbilical cord blood, and adipose tissue) are used in several preclinical and clinical trials, MSCs-based drug-delivery platforms could be considered as an attractive novel approach for tumor theranostics [6]
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