UBC Theses and Dissertations
Myelinating cells in repair of spinal cord injury Assinck, Peggy Lee
The damage inflicted by spinal cord injury (SCI) occurs in two phases. The primary injury is a mechanical insult to the spinal cord, resulting in permanent loss of cells and tissue structure. Multiple mechanisms of secondary injury extend this damage. One such mechanism is thought to be progressive loss of myelin, such that axons that survive primary injury are rendered dysfunctional by conduction block. As a result, myelin repair has emerged as a major research focus. The goals of this research were: i) to evaluate the extent of spontaneous repair by endogenous glia, and ii) to determine whether transplantation in a clinically relevant scenario can improve the outcome of SCI. In Chapter 2, I characterized the source and extent of spontaneous myelin repair in experimental SCI. I systematically assessed the cellular origin of new myelin and myelinating cells in transgenic mice, by genetically labeling multiple lineages prior to SCI. Contrary to prevailing dogma (that endogenous myelin repair was limited), we found that ~30% of myelinated axons at the injury epicentre were ensheathed de novo (since injury) at three months after SCI. In addition, the majority of myelinating Schwann cells (SCs) in the injured spinal cord were derived from oligodendrocyte precursor cells (OPCs) and infiltration of peripheral myelinating SCs made only a small contribution. In Chapter 3, I investigated the potential for improving spontaneous repair (and the outcome of SCI) through glial transplantation. Skin-derived precursor cells directed to a SC fate (SKP-SCs) were transplanted at the site of chronic SCI. At 21 weeks after transplantation (29 weeks-post SCI), SKP-SCs contained thousands of growing/regenerating axons, which were myelinated by either transplanted or endogenous SCs. The presence of endogenous SCs was increased after SKP-SC transplantation. Rats that received SKP-SCs had higher functional motor scores and displayed less bladder wall thickening (a hallmark of bladder dysfunction following SCI) compared to controls. These data contribute to our understanding of the endogenous glial repair response after SCI, both in the absence of treatment and following a clinically relevant cell transplantation. These endogenous repair mechanisms might be exploited and augmented to develop novel treatments for SCI.
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