Effects of Supermagnetic Iron Oxide Labeling on the Major Functional Properties of Human Mesenchymal Stem Cells from Multiple Sclerosis Patients

Abstract

Background and Objectives: In the last few years, treatment protocols using mesenchymal stem cells (MSC) in various experimental models and human diseases have been investigated. MSCs are on the focus of stem cell research, since they are considered as a type of adult stem cells with low toxicity and acceptable side effects profile and they can be administered autologously. In addition several studies have revealed significant immunomodulatory properties of MSCs and a potential for transdifferentiation, including neural differentiation, both in vivo and in vitro. Magnetic resonance imaging (MRI) is a non-invasive technique that can be used to track labeled cells and evaluate their migration ability in various clinical settings. Methods and Results: In this study we investigated whether such labeling of MSCs with the commercially used paramagnetic material, Feridex, has any negative effect on the above mentioned functional properties of MSCs. We labeled human mesenchymal stem cells (hMSC) with poly-L-lysine coated Feridex Ⓡ and evaluated their cellular differentiation and immunomodulatory properties, in vitro. In comparison with unlabeled cells, labeled hMSC exhibited normal adipogenic and osteogenic differentiation, but decreased chondrogenic differentiation. Regarding neural differentiation, labeled and unlabeled cells were similar in their ability to express neural-like and glial like surface proteins. Finally, both labeled and unlabeled MSCs exhibited a dose-dependent, significant blocking effect on the proliferation of healthy donors lymphocytes following mitogen stimulation. Conclusions: These findings indicate that labeling with Feridex does not affect the immunomodulatory, nor the neural transdifferentiation potential of MScs and therefore, Feridex may be used for the tracking of this type of stem cells in clinical applications, without compromising their major functional properties.

Cerebrospinal Fluid (CSF) Exchange with Artificial CSF Enriched with Mesenchymal Stem Cell Secretions Ameliorates Experimental Autoimmune Encephalomyelitis

“…MSCs transplantation alone has been applied and tested with strong indications of beneficial effects in animal models of MS [22,23,24,25], stroke [26,27], traumatic brain injury [28], PD [29], schizophrenia, and autism [30,31], with encouraging indications in pivotal clinical trials in MS and ALS patients [22,23,33,34,35]. Many of the beneficial effects of MSC have been shown to be mediated by humoral mechanisms and the secretion of neurotrophic and immunomodulatory factors [15,16,17,18,19,20,21].…”

“…MSCs produce a variety of neurogenic, neuroprotective, and immunomodulatory agents [15,16,17,18,19,20,21], and have been shown to induce beneficial effects when transplanted in EAE-mice [22,23,24,25], stroke [26,27], traumatic brain injury [28], Parkinson’s disease [29], schizophrenia, and autism [30,31] as well as increased neurogenesis in adult mice [32]. MSC transplantation also showed indications of efficacy in clinical trials in MS and ALS patients [22,23,33,34,35]. We use here secretions of MSCs of human origin, having the advantage of exploring its potential for future therapeutic purposes.…”

Noninvasive in vivo cell tracking using molecular imaging: A useful tool for developing mesenchymal stem cell-based cancer treatment

“…SPIO labeling may impact the proliferation, metabolic activity, viability, and overall morphology of MSCs, limiting their use[ 43 ]. Interestingly, Feridex (SPIO), a commercial paramagnetic material, demonstrated no effect on the physiological properties of MSCs, proposing their possible usefulness in the clinical setting[ 72 ]. Overall, SPIO labeling has low sensitivity and cannot detect the presence of a small number of cells[ 68 ].…”

Tracking Neural Progenitor Cell Migration in the Rodent Brain Using Magnetic Resonance Imaging

“…Labeling cells with iron oxide particles using these methods had no significant effect on cell viability or on ability to differentiate and migrate (Ben-Hur et al, 2007), especially at low (but still MR-visible) doses. However, some studies with mesenchymal stem cells (Bulte et al, 2004) have found differentiation along some lineages can be impaired; other studies have seen no effect (Arbab et al, 2005b; Kassis et al, 2010). Each cell type that is labeled in this way should be evaluated for effects on cell function prior to conducting studies in vivo .…”

“…Mesenchymal stem cells (MSC) can be obtained from patient and the use of such autologous grafts should reduce the likelihood of rejection (Akgun et al, 2015). MSC can be harvested in the operating room, cultured and labeled, then reintroduced into the targeted area of the patient (Callera and de Melo, 2007; Kassis et al, 2010). The importance of using autologous MSCs has not been definitively established (Kode et al, 2009).…”