Targeting Brain Tumors with Mesenchymal Stem Cells in the Experimental Model of the Orthotopic Glioblastoma in Rats.
Natalia M YudintcevaEkaterina LomertNatalia A MikhailovaElena N TolkunovaNikol AgadzhanianKonstantin SamochernychGabriele MulthoffGrigoriy TiminVyacheslav RyzhovVladimir DeriglazovAnton S MazurMaxim ShevtsovPublished in: Biomedicines (2021)
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.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- iron oxide
- magnetic resonance imaging
- induced apoptosis
- bone marrow
- drug delivery
- cell therapy
- pet imaging
- computed tomography
- high throughput
- cell cycle arrest
- magnetic resonance
- signaling pathway
- gene expression
- minimally invasive
- oxidative stress
- squamous cell carcinoma
- machine learning
- pain management
- endoplasmic reticulum stress
- molecularly imprinted
- fluorescent probe
- living cells
- cell proliferation
- smoking cessation
- replacement therapy
- mass spectrometry
- diffusion weighted imaging
- contrast enhanced
- lymph node metastasis
- squamous cell