Traumatic spinal cord injury (SCI) affects approximately 250,000 individuals in the U.S. Debilitating consequences include paralysis, sensory deficits, pain, lack of bladder control and loss of sexual function. One of the most promising therapies in the treatment of SCI is neural precursor cell (NPC) transplantation. NPCs differentiate into mature CNS cell types and consequently have the potential to replace and repair damaged tissue. The overall goal of the work presented in this thesis is to develop effective strategies for transplantation of NPCs into the injured spinal cord. Successful implementation of NPC transplantation is an extremely complicated problem, requiring a multi-faceted understanding of the challenges associated with cell grafting. Before NPC transplantation can be moved to the clinic, it is imperative to (1) understand the basic properties of NPC candidates (2) test their efficacy in valid models of SCI and (3) address practical issues related to clinical application of cell-based therapy. Once these and other critical questions are answered, we can more confidently design appropriate transplantation strategies for the treatment of SCI and other CNS pathologies in an informed and rationale manner. In Chapter 2, the fate of multipotent neural stem cells and lineage-restricted NPCs is compared following engraftment into the uninjured adult brain and spinal cord. In Chapter 3, the long-term fate of transplanted lineage-restricted NPCs is examined following engraftment into both the developing and adult brain and spinal cord. In Chapter 4, the fate of lineage-restricted NPCs is assessed following engraftment into the injured adult spinal cord, and their fate is compared to grafts of fetal spinal cord tissue. In Chapter 5, the behavioral and regenerative efficacy of lineage-restricted NPC grafts is examined using a lateral funiculotomy model of cervical SCI. In Chapter 6, an alternative cell delivery method, lumbar puncture, is tested for its ability to deliver lineage-restricted NPCs to the injured cervical spinal cord. In Chapter 7, the fate of lineage-restricted NPCs is non-invasively tracked using magnetic resonance imaging following engraftment into the uninjured adult spinal cord. Such a multi-faceted experimental approach is important for translation of NPC transplantation to the clinic.
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Details
Title
Neural precursor cell transplantation
Creators
Angelo Carmen Lepore
Contributors
Itzhak Fischer (Advisor) - Drexel University, Drexel University (1970-)
Awarding Institution
Drexel University
Degree Awarded
Doctor of Philosophy (Ph.D.)
Publisher
Drexel University; Philadelphia, Pennsylvania
Number of pages
xviii, 331 pages
Resource Type
Dissertation
Language
English
Academic Unit
Neurobiology and Anatomy; College of Medicine; Drexel University
Other Identifier
991021888826204721
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