Cell therapy is a promising strategy for the treatment of neurological diseases. Positive therapeutic effects have been obtained in animal models, and, recently, in a few clinical trials; however, the efficacy is still limited. Rather than intracerebral transplantation, body fluids, such as blood or CSF, are increasingly being used as a route of stem cell delivery to achieve a wider distribution of cells and to make the procedure less invasive. For circulating fluid-mediated cell transplantation, the improvement of cell homing to lesion sites is critical in advancing stem cell therapy. The optimization of cell delivery and targeting can be greatly accelerated with the use of non-invasive cellular imaging. Because of the high signal of iron oxide nanoparticles (SPIO) and the translational potential, MRI is the leading technology for in vivo cellular imaging. While MRI, because of its high spatial resolution, is unprecedented for the depiction of the location of transplanted cells, it does not provide information about cell viability. But, this can be complemented with reporter gene-based bioluminescent imaging (BLI) to image cell survival. MR imaging of SPIO-labeled human stem cells enables visualization of cell trafficking following intracarotid delivery. Transplantation of large, mesenchymal stem cells in a rat model of stroke resulted in early entrapment of cells in the ipsilateral hemisphere. The distribution of cells was dependent on the time from stroke induction to cell transplantation (1, 2, 3, and 7 days) and could be related to the evolution of blood supply to distinct compartments of this hemisphere over the first week after stroke. A massive outflow of cells from the brain was observed within the first day after transplantation. The transplantation of small, human glial restricted progenitors (GRPs) cells affected rat brain homing only if these cells were engineered to express VLA-4 integrin (VLA-4+), and the endothelium was activated by LPS to express VCAM-1, a receptor for VLA-4. The transplantation of VLA+ GRPs in a rat model of stroke affected the selective inflow of cells to the lesion and the persistence of the iron oxide signal for over a month. However, BLI revealed a gradual decrease of cell viability, with a loss of bioluminescence within one week after transplantation. The signal disappearance was thought to be the result of the rejection of human cells in non-immunosuppressed animals. The monitoring of cell fate post transplantation into the cerebral ventricles is also crucial, since the circulation of the CSF may affect the homing of transplanted cells. MR imaging of the intracerebroventricular (ICV) delivery of SPIO-labeled cells in a pediatric patient showed the feasibility of the procedure, with no adverse events and successful detection of SPIO-labeled cells. In this patient, in particular, cells transplanted to the frontal horn of the lateral ventricle were found in the occipital horn. Considering the patient position during surgery, such cell distribution could have resulted from cell sedimentation. The location of the cells was stable on follow-up MRIs, but a gradual disappearance of the SPIO signal was observed. ICV delivery in large animals (pig) revealed a more dispersed distribution of cells, which may be attributable to slit ventricles.
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