UBC Theses and Dissertations
Skin-derived precursors are a suitable alternative to peripheral nerve as a source of Schwann cells for transplantation-based repair of the injured rat spinal cord Sparling, Joseph Samuel
For much of human history the devastating loss of neurological functions that occurs after spinal cord injury (SCI) was thought to be irreversible, so the people afflicted with such injuries were offered no hope of effective medical treatment. Today that has changed, as advances in neurobiology and medicine over the past century have led to the development of treatments aimed specifically at repairing the injured spinal cord. The transplantation of Schwann cells (SCs) has emerged as one promising example of such a treatment, with demonstrated efficacy in multiple animal models of SCI and encouraging preliminary results in clinical trials. Although SCs possess many of the qualities of an ideal cellular therapy, the harvest of autologous SCs from peripheral nerve (N-SCs) causes permanent nerve injury, which could be avoided by generating SCs from an alternative autologous source. One such source is skin-derived precursors (SKPs), which can be isolated from the adult mammalian dermis and differentiated into SCs (SKP-SCs) in vitro. Herein I examined the efficacy of SKP-SCs as a treatment for SCI in rodent injury models and compared those cells to their nerve-derived counterparts. This work provided the first demonstration of efficacy for SKP-SC therapy after thoracic contusion and showed that, much like N-SCs, SKP-SCs myelinate, promote axonal growth, and enhance functional recovery after SCI. In addition, we found evidence that SKP-SCs may have advantages over N-SCs with respect to their ability to interact favourably with spared astrocyte-rich host tissue and promote axonal growth. Subsequently we directly compared neonatal SKP-SCs and N-SCs and found that those cell types were highly similar in terms of their protein/gene expression profiles, migration and integration into astrocyte-rich domains in vitro and in vivo, and many reparative effects following transplantation into the partially crushed cervical spinal cord. Taken together our findings suggest that SKP-SCs and N-SCs have similar therapeutic efficacy, and that where differences between those two cell types exist, they consistently favour the SKP-SCs as the more favourable cell type for SCI repair. Thus, our work to-date supports the notion that SKP-SCs are a suitable alternative to N-SCs for transplantation-based central nervous system repair.
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