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Rounding the implant.To enable in vivo detection of the graft, cells were labeled before transplantation with PLL-SPIO nanoparticles. Several studies have used magnetically labeled cells to monitor the fate of transplanted cells within the organism [22,32,33]. Cells labeled with iron-oxide nanoparticles (at a similar concentration) can migrate, differentiate, and improve functional outcome in different diseases [11,34]. It is possible to monitor SPIOlabeled neural stem cells for 18 weeks after transplantation [35]. The cells can differentiate into neuronal and glial lineages and Staurosporine have neuronal-like electrophysiological characteristics, with no signs of tumor formation. Similarly, subventricular zone (SVZ) cells labeled by ferromagnetic particles were transplanted intracisternally into a rat model of stroke. The transplanted cells selectively migrated toward the ischemic parenchyma, and the grafted animals exhibited significant improvement of their neurologic function [36]. In our experiments, we followed the animals by using MRI only for 8 weeks. The graft was clearly visible at the cranial side of the lesion, although the labeling efficiency was only 57 . By 8 weeks after transplantation, the transplanted cells were mainly nestin- and GFAP-positive, no matter whether the cells were nanoparticle-labeled or not. Also, no difference was observed in behavioral tests between animals that were transplanted with labeled or unlabeled cells. However, the morphometric evaluation of the spared white and gray matter, as well as the qPCR analyses, were performed in animals grafted with unlabeled cells, although it was shown that the secretion profile of ferumoxide-labeled human bone marrow, mesenchymal cells was not impaired by the labeling, including the production of growth factors and cytokines mediating the recovery effect [37]. To study more precisely the effect of SPIO nanoparticles on in vivo differentiation and the dynamics of nanoparticle expulsion, further long-term studies would have to be performed. We have seen functional improvement as early as 3 weeks after transplantation. However, 5 weeks later (that is, 8 weeks after transplantation), grafted SPC-01 cells still expressed mainly progenitor markers, such as Olig2, nestin, and NSE, and were GFAP positive. Conversely, at this same time, the robust sprouting of endogenous neurons, positive for GAP43, was observed, most likely dueto a paracrine effect of the graft by which the expression of the NGF gene was significantly upregulated. Moreover, the transplantation of SPC-01 cells led to the upregulated expression of the rat neurotrophin genes PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16989806 Nt3 and Ngf compared with lesioned control animals. Neurotrophic factors such as NGF, BDNF, and NT3 play critical roles in axonal growth and in the survival of existing neurons [38-41]. Consistent with these reports, we observed that SPC-01 cell transplantation promoted functional recovery after SCI. Therefore, we suggest that the early significant improvement in motor and sensory tests was mediated by the increased expression of neurotrophic factors by the transplanted SPC-01 cells, especially NGF. Human cells, although they are transplanted into rodent tissue, mature much more slowly than their mouse or rat counterparts. A similar effect was observed in our study when NSCs derived from human iPS cells were injected into animals with middle cerebral artery occlusion (a model of stroke). Functional outcome and the protection of the host substantia ni.