MRI tracking of polyethylene glycol-coated superparamagnetic iron oxide-labelled placenta-derived mesenchymal stem cells toward glioblastoma stem-like cells in a mouse model

Abstract

Mesenchymal stem cells (MSCs) that display homing and infiltration properties towards tumor cells are a promising cellular targeting vector for brain tumor therapy but are limited to local-regional delivery in current preclinical models. Here, we investigated whether placenta-derived MSCs (P-MSCs) are a superior cellular vector for systemic targeting of glioblastoma stem-like cells (GSCs), with an imaging modality to real-time monitor the trafficking P-MSCs to glioblastoma sites. Results demonstrated that P-MSCs had greater migratory activity towards GSCs and across blood-brain barrier compared with bone marrow-derived MSCs, and this activity was enhanced by hypoxia precondition. Chemokine ligand 5 was identified as a chemoattractant responsible for the glioblastoma tropism of P-MSCs. Polyethylene glycol-coated superparamagnetic iron oxide (PEG-SPIO) was synthesized for cellular labelling and imaging P-MSCs, displaying high cellular uptake and no cytotoxic effect on P-MSCs cell proliferation or stemness property. The homing effects of intravenously administered PEG-SPIO-labelled P-MSCs towards intracerebral GSCs were able to be detected in mice models through T2-weighted magnetic resonance imaging (MRI). This study suggests the possibility of innovative systemic P-MSC-based cell therapy for aggressive GSCs, developing a state-of-the-art theranostic technique for real-time tracking of therapeutic P-MSCs tumor infiltration through cellular MRI.

Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies

“…The main and most used are bioluminescent optical imaging (BLI), magnetic resonance imaging (MRI), and nuclear imaging techniques. [50][51][52][53][54][55] For a in-depth review on MSC homing imaging, see Reference 43. In a syngeneic rat model, luciferase charged MSCs, injected in the right common carotid artery, were tracked by in vivo BLI into right frontal lobe, co-localizing with glioma cells. Similar results were observed using a fluorescent vital dye, after injection into the same site.…”

“…50,54 Migration of AT-MSCs to target brain tumor-initiating cells was studied by in vivo BLI analysis using fluorescent magnetic nanoparticles. 52,56 57,58 promoting macrophages transformation from M1 to M2 anti-inflammatory phenotype, 59 or contributing to immune homeostasis. MSCs also modulate maturation and functions of dendritic, 60 B, 61 and NK cells.…”

“…Alongside these techniques, whole body imaging methods have been developed and allowed to study the kinetics and the distribution of MSCs in live animals. The main and most used are bioluminescent optical imaging (BLI), magnetic resonance imaging (MRI), and nuclear imaging techniques 50‐55 . For a in‐depth review on MSC homing imaging, see Reference 43.…”

“…Other technical studies validate the use of gold‐coated nanoparticles or ferritin heavy chain expressing MSCs as marker to track by MRI 50,54 . Migration of AT‐MSCs to target brain tumor‐initiating cells was studied by in vivo BLI analysis using fluorescent magnetic nanoparticles 52,56 . Hsu et al demonstrated that hypoxia‐preconditioned placental‐derived MSCs (p‐MSCs) pass BBB and reach intracranial U87‐GBM stem cells in mice.…”

Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

“…Stem cells have risen as a promising therapeutic option for the treatment of malignant gliomas, as they would be able to migrate and home into glioma tumors, including microscopic tumor foci, which harbor the potential to seed future recurrence (Brown et al, 2003;Nakamura et al, 2004;Kim et al, 2005Kim et al, , 2018Sonabend et al, 2008;Thu et al, 2009;Yong et al, 2009;van Eekelen et al, 2010;Amano et al, 2011;Choi et al, 2011;Kleinschmidt et al, 2011;Ryu et al, 2011;Altanerova et al, 2012;Jiao et al, 2012;Kosaka et al, 2012;Cheng Y. et al, 2013;Huang et al, 2013Huang et al, , 2014Lee et al, 2013;Balyasnikova et al, 2014;Li et al, 2014;Mooney et al, 2014b;Bryukhovetskiy et al, 2015;de Melo et al, 2015;Martinez-Quintanilla et al, 2015;Morshed et al, 2015;Park et al, 2015;Cheng S. H. et al, 2016;Liu et al, 2016;Mangraviti et al, 2016;Muroski et al, 2016;Meca-Cortes et al, 2017;Portnow et al, 2017;Hsu et al, 2018;Lang et al, 2018;Pavon et al, 2018;Tirughana et al, 2018;Zhang et al, 2018;Huang R. Y. et al, 2019;…”