Grant: Collaborative Health Research Projects (NSERC partnered)

Spinal cord injury (SCI) destroys neural tissue and can render patients severely disabled. Lack of recovery after SCI is associated with the inability of the injured neural tissue to repair or regenerate itself. To overcome the devastation of SCI, stem cells have been used to supplement the destroyed cell populations and restore functions. However, other than often contested ethical issues such as procurement of stem cells, limited supply and survival of viable stem cells, immuno-rejection of exogenous stem cells, and poorly controlled in vivo proliferation and differentiation of transplanted stem cells are all impediments to clinical applications of this approach. Therefore, we propose to develop a novel hollow fiber channel (HFC) to allow recruitment, propagation and differentiation of endogenous neural stem cells to repair SCI. This novel biodegradable HFC will be engineered to stimulate the recruitment of endogenous stem cells from the local host tissues to repair the spinal cord. By recruiting the patient's own endogenous stem cells for repair, the ethical and rejection issues are eliminated. The channel design incorporates the essential growth factors within the HFC wall and allows the sequential administration of the growth factors, to first enable endogenous stem cell propagation and then differentiation. To achieve this, the HFC will be composed of three-layered wall with growth factor delivery controlled by varying each layer's porosity and degradation properties. To assess the efficacy of this approach, the HFCs will be used in an acute complete spinal cord lesion rat model. The spinal cords of the implanted animals will be obtained at pre-determined time points after implantation to assess the extent of endogenous stem cell proliferation and differentiation. In addition, rats will be assessed with magnetic resonance imaging (MRI), functional locomotor testing, electrophysiology and histology. It is estimated that there are about 400,000 people who live with SCI in North America and that the cost of care of these patients exceeds $10 billion annually.