The increasing number of studies focusing on regenerative me

The increasing number of studies focusing on regenerative medicine and stem cell transplantation is being accompanied by the development of techniques using many types of nanoparticles. The combination of nanotechnology with stem cell research may be able to address some challenges in this research field, including stem cell monitoring after transplantation. Since most experimental cell-tracking techniques require histological analysis, non-invasive approaches to assess migration, fate and integration of transplanted cells represent a significant advance for the clinical application of biomedical treatments using stem cells. MRI of magnetically labeled cells is an emerging technology that offers excellent resolution in vivo. SPION are negative contrast agents that render transplanted stem cells trackable when imaged with the appropriate pulse sequence. These nanoparticles consist of magnetite (iron oxide) cores, which are coated with dextran or siloxanes encapsulated by a polymer or further modified to facilitate internalization (Jung and Jacobs, 1995; Rogers et al., 2006). Our group has recently shown that SPION-labeling does not affect viability, proliferation and differentiation of MSC (Jasmin et al., 2010) and we have now applied the same technique to track MSC in vivo in a rat model of Huntington\'s disease. Moreover, to investigate the neuroprotective potential of MSC in HD it is important to evaluate the effect before massive cell death. In this report, we implanted SPION-labeled MSC into the striata of rats 1h after QUIN injection, to investigate their neuroprotective effects and to monitor their fate over the long term.
Methods
Results
Discussion MSC are known to play a therapeutic role in tranylcypromine Supplier lesions, and can be safely cultured in vitro with no risk of malignant transformation (Bernardo et al., 2007; Uccelli et al., 2008). This is the first time that a therapeutic effect of MSC in HD with transplantation 1h after QUIN lesions, and using a specific neurodegenerative marker, has been shown. We demonstrated that local MSC delivery has neuroprotective effects in a rat model of HD, leading to reduced striatal neurodegeneration and decreasing ventriculomegaly after QUIN injection. Furthermore, we demonstrated the feasibility of SPION labeling, and cells loaded with SPION were monitored in vivo in the striata of QUIN-lesioned rats. We used FJ-C to evaluate the chronology of cellular death in the QUIN model and the effects of MSC on neurodegeneration. FJ-C is a good marker of degenerating neurons, and stains all types of cell death. Previous findings have indicated a peak at the third day, with reduced staining on the fifth day after lesion, using Transferase Biotin-dUTP Nick End Labeling (TUNEL) (Bordelon et al., 1999). We found a peak of FJ-C cells from 1 to 3days after QUIN injection. This pattern might reflect the acute characteristic of QUIN-mediated lesion and the high sensitivity of FJ-C in acute neuronal injury, in contrast to its low sensitivity in delayed assessment of damage (Lee et al., 2010). Because most cells die in the first days after QUIN, we tested the neuroprotective potential of MSC transplanted early after the insult. The first hours might be critical in saving damaged tissue, since DNA fragmentation that indicates cellular death is detected 1h after QUIN (Dure et al., 1995). It is possible that a similar effect would be achieved if patients could be treated in the initial phase of the disease. We found significantly reduced striatal neurodegeneration in lesioned rats 7days after transplantation. This result may be related to a paracrine effect of MSC, which might serve to inhibit the progression of damage, as reviewed by others (Le Blanc and Ringden, 2007; Uccelli et al., 2007). MSC are known to release neurotrophic factors that are important for neuronal survival and growth (Caplan and Dennis, 2006). Moreover, numerous reports have revealed that MSC have immunomodulatory properties, including suppression of T-cell proliferation (Aggarwal and Pittenger, 2005; Di Nicola et al., 2002), inhibition of resting natural killer cytotoxic activity (Liu et al., 2009; Sotiropoulou et al., 2006) and microglial activation (Lee et al., 2009).