Cellular therapy after spinal cord injury using neural progenitor cells

Vroemen, Maurice (2006)

Doctoral Thesis

In this thesis, the possibilities and limitations of cell-based therapies after spinal cord injury are explored. Particularly, the potential of adult derived neural progenitor cell (NPC) grafts to function as a permissive substrate for axonal regeneration was investigated. It was found that syngenic adult derived neural progenitor cells are able to survive transplantation in the acutely lesioned spinal cord and differentiate into glial phenotypes. When co-grafted with fibroblasts, glial fibrillary acidic protein expressing grafted NPC are able to replace the lesion defect and are able to induce contact mediated axon guidance and regenerative sprouting. NPC that are co-grafted with highly purified Schwann cells however migrate away from the lesion site, which is paralleled with a reduced axonal outgrowth. A close investigation of NPC that are transduced to express ectopic genes by using different viral vectors revealed that in vivo gene expression in genetically engineered neural progenitor cells is temporally limited and mostly restricted to undifferentiated NPC. Finally, MRI imaging at 17.6 Tesla was used to in vivo monitor structural changes following spinal cord injury in rats, enabling future longitudinal studies that allow direct correlation of structure with function.

• Rat
• Transplantation
• CNS
• Schwann cells
• Axon
• Glia
• Regeneration
• Gene therapy

• All authors: Vroemen, Maurice
• Supervisor: Marani, E.; Winkler, J.
• Co-supervisor: Weidner, N.
• Qualification: Doctor (dr.)
• Awarding Institution: Department of Neurosurgery, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2006-01-17