462 Stem Cell-Loaded Implantable Intrathecal Bioreactors for the Treatment of Spinal Cord Injury: A Porcine Model Pilot Study

Abstract

INTRODUCTION: Stem cells promote spinal cord injury (SCI) recovery by secreting paracrine factors that orchestrate endogenous healing mechanisms. However, effects in clinical trials are modest and there are no approved stem cell therapies to treat SCI. Major barriers include cell washout, immune attack, and oncogenic potential. METHODS: ITBs were implanted in three pigs. One pig received a cell-loaded ITB without injury (Cells), another received a cell-loaded ITB with injury (Cells + SCI), and another received a sham ITB with injury (SCI). SCIs were induced by weight drop at T5. ITBs were implanted cranial to the injury and sutured under the dura then loaded with human mesenchymal stem cells or sham cell media. Cerebrospinal fluid (CSF) was collected for 6 days following surgery through a lumbar drain. Cytokines in the CSF were measured by ELISA and the ITB was retrieved for cell viability staining. RESULTS: Upon retrieval, stem cells were alive on viability staining of the ITB. CSF levels of the pro-inflammatory cytokines IFNy and IL-1a were increased in the SCI condition compared to the Cells and Cells + SCI conditions. Pro-inflammatory cytokines peaked on post-operative day 5 and remained high. Anti-inflammatory cytokines IL-1ra, VEGF, and TGFβ were elevated in the SCI + Cells condition and depressed in the SCI condition compared to the Cells condition. Anti-inflammatory cytokines peaked on post-operative day 3 and decreased by day 6. CONCLUSIONS: In this pilot study, stem cells survived in an implantable ITB and altered cytokine levels in the CSF of pigs with SCI. Cell-loaded ITBs reduced pro-inflammatory cytokines and increased anti-inflammatory cytokines. Implantable ITBs warrant further study as they may represent a potential new delivery option for stem cell therapy.