Abstract
Multipotent stem cells (SCs) could substitute damaged cells and also rescue degeneration through the secretion of trophic factors able to activate the endogenous SC compartment. Therefore, fetal SCs, characterized by high proliferation rate and devoid of ethical concern, appear promising candidate, particularly for the treatment of neurodegenerative diseases. Super Paramagnetic Iron Oxide nanoparticles (SPIOn), routinely used for pre-clinical cell imaging and already approved for clinical practice, allow tracking of transplanted SCs and characterization of their fate within the host tissue, when combined with Magnetic Resonance Imaging (MRI). In this work we investigated how SPIOn could influence cell migration after internalization in two fetal SC populations: human amniotic fluid and chorial villi SCs were labeled with SPIOn and their motility was evaluated. We found that SPIOn loading significantly reduced SC movements without increasing production of Reactive Oxygen Species (ROS). Moreover, motility impairment was directly proportional to the amount of loaded SPIOn while a chemoattractant-induced recovery was obtained by increasing serum levels. Interestingly, the migration rate of SPIOn labeled cells was also significantly influenced by a degenerative surrounding. In conclusion, this work highlights how SPIOn labeling affects SC motility in vitro in a dose-dependent manner, shedding the light on an important parameter for the creation of clinical protocols. Establishment of an optimal SPIOn dose that enables both a good visualization of grafted cells by MRI and the physiological migration rate is a main step in order to maximize the effects of SC therapy in both animal models of neurodegeneration and clinical studies.
Highlights
Nanomedicine has a leading role in pharmaceutical research and development of clinical protocols, mainly in the form of nanoparticle-based delivery systems for drugs and imaging agents, especially in the field of stem cell (SC) therapies [1]
Several functionalized nanoparticle formulations have been proposed for medical applications, but few of them have been approved by the Food and Drug Administration (FDA), mainly because of reproducibility problems and uncertain stability in the long term coupled to the absence of consensus guidelines on the required biological testing [2,3]
No significant differences were found in the number of cells in culture at different time points (T0, T3, T6 T10 and T13) between loaded and unloaded hCVCs, demonstrating that Super Paramagnetic Iron Oxide nanoparticles (SPIOn) did not altered the cell growth rate (Fig. 1 a)
Summary
Nanomedicine has a leading role in pharmaceutical research and development of clinical protocols, mainly in the form of nanoparticle-based delivery systems for drugs and imaging agents, especially in the field of stem cell (SC) therapies [1]. Several functionalized nanoparticle formulations have been proposed for medical applications, but few of them have been approved by the Food and Drug Administration (FDA), mainly because of reproducibility problems and uncertain stability in the long term coupled to the absence of consensus guidelines on the required biological testing [2,3]. Ferumoxides (a suspension of Super Paramagnetic Iron Oxide nanoparticles (SPIOn)), are (FDA)-approved agents which may be accurately, sensitively and detectable by non-invasive Magnetic Resonance Imaging (MRI) to monitor grafted cell distribution over time [4]. U.S and European governments are promoting study programs on the impact of nanotechnology and the potential risks of nanoparticles (United States Enviromental Protection Agency (EPA), Nanotechnology & Nanomaterials Research, http://www.epa.gov/nanoscience/ index.htm)
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