2140 Repeated Intramedullary Transplantation of Allogeneic Porcine Neural Stem Cells Into the Porcine Spinal Cord Increased Immune Response, But Did Not Compromise Graft Survival

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INTRODUCTION: Transplantation of stem cells into the central nervous system (CNS) has shown promising results for several indications. Future therapies may require staged or repeated transplantation, but there is no data to support the feasibility of this approach nor an understanding of the immunological consequences. METHODS: Porcine fetal spinal cord-derived neural stem cells (pNSCs) transfected with GFP were used were transplanted into the spinal cord of ten Göttingen minipigs in a staged strategy. Five pigs underwent laminectomy and intramedullary thoracolumbar transplantation followed by cervical transplantation of pNSCs three weeks later. For control, five pigs underwent intramedullary thoracolumbar infusion of 20 µL of transplantation medium (control) followed by cervical transplantation of pNSCs three weeks later. 10 grafts of 2.0 × 105 pNSCs were transplanted per segment into the ventral horn using a stereotactic platform. Three weeks after the second procedure, animals were sacrificed, and tissue harvested for immunohistochemistry and quantitative stereology. RESULTS: No difference in transplanted cell graft survival was identified between lumbar or cervical grafts in the experimental arm, nor with cervical grafts in the control arm (P > 0.05). Second stage cervical transplants in the experimental group exhibited a significant increase in infiltration of CD8+ T lymphocytes compared to control group cervical transplants (p = 0.0079) and first stage lumbar transplants (p = 0.0159). There was also a significant increase in infiltration of CD4+ cells in experimental cervical grafts compared to control cervical grafts (p = 0.0317). CONCLUSIONS: This study is the first to report on repeated stem cell transplantation in the CNS. We showed stable cell graft survival, but increased infiltration of CD4+ and CD8+ T lymphocytes with repeated transplantation. This novel study provides critical information regarding the feasibility of repeated transplantation into the CNS.

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