Our goal is to promote regeneration and recovery of function after spinal cord injury by identifying the best strategies for cellular transplantation and to apply gene therapy methods to introduce therapeutic genes into the injured spinal cord. We are currently studying the efficacy of genetically modified fibroblasts, multipotential neural stem cells, neural and glial precursors, and bone marrow stromal cells.
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Gene Therapy / Genetically Modified Fibroblasts We use retrovirus and adenovirus vectors to genetically modify cells and deliver neurotrophin genes as a strategy of promoting survival of injured neurons and axon regeneration. We have modified fibroblasts using a retrovirus containing neurotrophic genes neurotrophin-3 (NT-3) or brain derived neurotrophic factor (BDNF) and a marker gene, allowing us to track genetically modified cells via various staining methods. |
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Neural Stem Cells and Progenitors We study the properties of multipotential neural stem cells (NEP) as well as neuronal restricted precursors (NRP) and glial restricted precursors (GRP) and we test their therapeutic potential following grafting into the injured adult spinal cord (Han and Fischer, 2001). Neural stem cells do not survive or differentiate into neurons well in the adult system. Our transplantation experiments address fundamental issues of the potential and fate of neural stem cells and lineage restricted progenitors, as well as the development of therapeutic strategies for the repair of spinal cord injury. |
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Bone Marrow Stromal Cells The use of human marrow stromal cells (MSC), an adult stem cell, is promising because MSCs can be obtained from the bone marrow of spinal cord injury patients. Our grafting experiments of these cells into the injured spinal cord demonstrated that they produce a permissive environment for growing axons, and may, therefore, have potential for clinical application. |
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Structure and Function of the Neuronal Cytoskeleton We also study the expression and function of cytoskeleton proteins, particularly microtubule proteins in the nervous system during development and regeneration in both the PNS and CNS. We use biochemical, cellular, and molecular approaches that include inhibition by antisense oligonucleotides, microinjection of recombinant antibodies, analysis of transcriptional regulation and transgenic animal. We study the role of MAP1B and tau in axonal growth and the mechanism of their phosphorylation and possible application of these genes to improve regeneration. |
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