Abstract
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.
Highlights
Spinal cord injury (SCI) could affect the distribution of materials in cerebrospinal fluid (CSF). To address these subjects further, we injected Cy5.5 fluorescent dye or cells labelled with fluorescent magnetic nanoparticles (FMNPs) into lateral ventricle (LV) of rats with or without SCI in this study and analyzed their in vivo distributions using in vivo optical imaging techniques
We detected in vivo signal of Cy5.5 fluorescent dye utilizing in vivo optical imaging techniques in the central nervous system (CNS) of rats with or without SCI (SCI and normal group, respectively, n = 5 for each group) at 24 hours after injection into the lateral ventricle (LV)
When Cy5.5 fluorescent dye and FMNP-labelled U87MG signal of normal and SCI groups were compared (n = 5 for each group, Fig 3), these four groups showed similar quantitative distributions of signals. This suggests that distributions in the CNS of soluble Cy5.5 fluorescent dye and colloidal FMNP-labelled U87MG cells are similar when they are injected into CSF of the LV
Summary
To simulating clinical situation in animal models, we have injected Cy5.5 fluorescent dye into the lateral ventricle (LV) or cisterna magna (CM) of rat without SCI and compared its in vivo distribution in each region of spinal cord [11]. To address these subjects further, we injected Cy5.5 fluorescent dye or cells labelled with fluorescent magnetic nanoparticles (FMNPs) into LVs of rats with or without SCI in this study and analyzed their in vivo distributions using in vivo optical imaging techniques.
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