In vivo distribution of U87MG cells injected into the lateral ventricle of rats with spinal cord injury
Stem cells could be the next generation therapeutic option for neurodegenerative diseases including spinal cord injury (SCI). However, several critical factors such as delivery method should be determined before their clinical applications. Previously, we have demonstrated that lateral ventricle (LV) injection as preclinical simulation could be used for intrathecal administration in clinical trials using rodent animal models. In this study, we further analyzed in vivo distribution of cells that were injected into LVs of rats with SCI at thoracic level using in vivo imaging techniques. When 5 × 106 U87MG cells labelled with fluorescent magnetic nanoparticle (FMNP-labelled U87MG) were administrated into LVs at 7 days after SCI, FMNP-labelled U87MG cells were observed in all regions of the spinal cord at 24 hours after the injection. Compared to water-soluble Cy5.5 fluorescent dye or rats without SCI, in vivo distribution pattern of FMNP-labelled U87MG cells was not different, although migration to the spinal cord was significantly reduced in both Cy5.5 fluorescent dye and FMNP-labelled U87MG cells caused by the injury. The presence of FMNP-labelled U87MG cells in the spinal cord was confirmed by quantitative PCR for human specific sequence and immunohistochemistry staining using antibody against human specific antigen. These data indicate that LV injection could recapitulate intrathecal administration of stem cells for SCI patients. Results of this study might be applied further to the planning of optimal preclinical and clinical trials of stem cell therapeutics for SCI.
