Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters

Abstract

cell tracking with magnetic resonance imaging (MRi) is important for evaluating the biodistribution of transplanted cells. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a promising therapeutic tool in regenerative medicine. We examined the Uc-MScs labeled with superparamagnetic (Spio) and ultrasmall superparamagnetic iron oxide (USpio) in terms of cell functioning and imaging efficiency in vitro and in vivo. The UC-MSCs were co-incubated with SPIO or USPIO at a concentration of 50 or 100 µg/mL of label. Viability and proliferation were assessed by Trypan blue dye exclusion and MTT assay, respectively. Differentiation (chondrogenesis, osteogenesis, and adipogenesis) was induced to examine the impact of labelling on stemness. for in vitro experiments, we used 7-T MRI to assess the T 2 values of phantoms containing various concentrations of cell suspensions. For in vivo experiments, nine neonatal rats were divided into the control, SPIO, and USPIO groups. The UC-MSCs were injected directly into the rat brains. MRI images were obtained immediately and at 7 and 14 days post injection. The UC-MSCs were successfully labeled with SPIO and USPIO after 24 h of incubation. Cell viability was not changed by labelling. Nevertheless, labelling with 100 µg/mL USPIO led to a significant decrease in proliferation. The capacity for differentiation into cartilage was influenced by 100 µg/mL of SPIO. MRI showed that labeled cells exhibited clear hypointense signals, unlike unlabeled control cells. In the USPIO-labeled cells, a significant (P < 0.05) decrease in t 2 values (= improved contrast) was observed when compared with the controls and between phantoms containing the fewest and the most cells (0.5 × 10 6 versus 2.0 × 10 6 cells/mL). In vivo, the labeled cells were discernible on T 2-weighted images at days 0, 7, and 14. The presence of SPIO and USPIO particles at day 14 was confirmed by Prussian blue staining. Microscopy also suggested that the regions occupied by the particles were not as large as the corresponding hypointense areas observed on MRI. Both labels were readily taken up by the UC-MSCs and identified well on MRI. While SPIO and USPIO provide improved results in MRI studies, care must be taken while labelling cells with high concentrations of these agents. Mesenchymal stem cells (MSCs), a kind of somatic stem cells, are isolated from the mesenchymal tissues, such as fat, bone, and cartilage. MSCs can differentiate into mesodermal cells 1 , endodermal 2 , and ectodermal cells 3. Because of their regenerative and immunoregulatory capacities 4 , MSCs are expected to be applied for the therapy of various diseases, such as osteogenesis imperfecta, ischemic stroke, and cardiac infarction. Bone marrow is the most common source of MSCs. However, collecting MSCs from the bone marrow is highly invasive, and the maximal life span of the cells is affected by the donor's age 5. Currently, an umbilical cord tissue called Wharton's jelly is attracting attention, as a promising source of stem cells becaus...

Biodistribution of Mesenchymal Stromal Cells after Administration in Animal Models and Humans: A Systematic Review

“…The ability of MSCs to migrate from one hemisphere to another has also been demonstrated in other studies [87]. In other reports [88][89][90][91][92][93], MSCs injected intracerebrally were detectable at the site of administration 1-3 weeks after injection, with a subsequent rapid decrease and no significant systemic distribution. Other studies [94] showed that MSCs can be detected with fluorescence and bioluminescence up to 7 weeks after transplantation; (c) Intraventricular injection of MSCs: Some studies showed that MSCs injected into cerebral ventricles are able to migrate to large blood vessels in a brain traumatic injury model [95], and also to brain parenchyma and the spinal cord [96].…”

Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications

“…Magnetic resonance imaging (MRI) can be used to track MSCs in vivo by labeling MSCs with superparamagnetic iron oxide nanoparticles (SPIONs) or fluorine-19 ( 19 F). Direct labeling of MSCs with SPIONs is possible as these agents are readily taken up by MSCs and show up as hypointense signals on MRI [ 247 ]. However, some studies have shown that proliferative and differentiation capabilities of MSCs could be affected when labeled at higher concentrations [ 247 ].…”

“…Direct labeling of MSCs with SPIONs is possible as these agents are readily taken up by MSCs and show up as hypointense signals on MRI [ 247 ]. However, some studies have shown that proliferative and differentiation capabilities of MSCs could be affected when labeled at higher concentrations [ 247 ]. The downside of SPION labeling is that the specificity of SPION-labeled cells could be low and the signals could be hard to differentiate from acutely injured tissues containing hemorrhages.…”

Hybrid System for Local Drug Delivery and Magnetic Hyperthermia Based on SPIONs Loaded with Doxorubicin and Epirubicin

“…Over the past several years, there has been a great development of iron oxide-based magnetic nanoparticles application in many scientific fields, including biomedical engineering [ 1 , 2 ], cell labeling [ 3 , 4 ], cancer treatment [ 5 , 6 , 7 ], magnetic drug delivery [ 8 , 9 ], multimodal imaging [ 10 , 11 ], and Magnetic Resonance Imaging (MRI) contrast agents [ 12 , 13 , 14 ], due to their unique and diverse biomedical properties. Depending on their composition and surface modification, they recently focused attention on the targeted anticancer treatment and mild magnetic hyperthermia (MH) [ 15 , 16 , 17 ].…”