Abstract
BackgroundMagnetic resonance imaging (MRI) is a promising tool for monitoring stem cell-based therapy. Conventionally, cells loaded with ironoxide nanoparticles appear hypointense on MR images. However, the contrast generated by ironoxide labeled cells is neither specific due to ambiguous background nor quantitative. A strategy to overcome these drawbacks is 19F MRI of cells labeled with perfluorocarbons. We show here for the first time that human neural stem cells (NSCs), a promising candidate for clinical translation of stem cell-based therapy of the brain, can be labeled with 19F as well as detected and quantified in vitro and after brain implantation.Methodology/Principal FindingsHuman NSCs were labeled with perfluoropolyether (PFPE). Labeling efficacy was assessed with 19F MR spectroscopy, influence of the label on cell phenotypes studied by immunocytochemistry. For in vitro MRI, NSCs were suspended in gelatin at varying densities. For in vivo experiments, labeled NSCs were implanted into the striatum of mice. A decrease of cell viability was observed directly after incubation with PFPE, which re-normalized after 7 days in culture of the replated cells. No label-related changes in the numbers of Ki67, nestin, GFAP, or βIII-tubulin+ cells were detected, both in vitro and on histological sections. We found that 1,000 NSCs were needed to accumulate in one image voxel to generate significant signal-to-noise ratio in vitro. A detection limit of ∼10,000 cells was found in vivo. The location and density of human cells (hunu+) on histological sections correlated well with observations in the 19F MR images.Conclusion/SignificanceOur results show that NSCs can be efficiently labeled with 19F with little effects on viability or proliferation and differentiation capacity. We show for the first time that 19F MRI can be utilized for tracking human NSCs in brain implantation studies, which ultimately aim for restoring loss of function after acute and neurodegenerative disorders.
Highlights
To achieve translation of experimental stem cell-based therapy into the clinic, non-invasive imaging modalities are necessary tools
We show for the first time that 19F Magnetic resonance imaging (MRI) can be utilized for tracking human neural stem cells (NSCs) in brain implantation studies, which aim for restoring loss of function after acute and neurodegenerative disorders
Culturing of human neural stem cells NSCs were obtained from the ganglionic eminences of an 8
Summary
To achieve translation of experimental stem cell-based therapy into the clinic, non-invasive imaging modalities are necessary tools. One such modality, magnetic resonance imaging (MRI), provides true three-dimensional data at high spatial resolution, enabling good detection of even small cell numbers in the living, intact individual. Contrast is achieved through in vitro labeling of cells with superparamagnetic iron oxide (SPIO) nanoparticles [1,2,3]. A rapidly emerging field to overcome these drawbacks of ambiguity of contrast assignment and cell quantification is cell labeling with perfluorocarbon (PFC) nano-emulsions, which can be detected with 19F MRI [7,8,9]. Magnetic resonance imaging (MRI) is a promising tool for monitoring stem cell-based therapy. We show here for the first time that human neural stem cells (NSCs), a promising candidate for clinical translation of stem cell-based therapy of the brain, can be labeled with 19F as well as detected and quantified in vitro and after brain implantation
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