A number of cell types have been used for cell transplantation studies in animal models to remyelinate demyelinated regions of the central nervous. These include committed myelin-forming cells such as oligodendrocytes and Schwann cells as well as precursor cells derived from either embryonic or adult brain. Recently cells within bone marrow have been shown to have the potential to differentiate into myelin-forming cells and to form myelin in animal models of demyelination upon direct injection into the lesion. We have recently shown that intravenous delivery of bone marrow cells can target a chemically-induced demyelination site in the rat spinal cord and remyelinate these axons. This opens the intriguing prospect of delivery of cells to systemically target sites of demyelination and to achieve myelin repair. The precise cell type within this fraction of bone marrow is not known, nor is the full repair potential of this approach understood. In this proposal we will study isolated bone marrow stromal cells (MSCs) to quantify remyelination induced by direct intraspinal and intravenous delivery of the MSCs to determine the extent to which we can repair a demyelinated lesion. These results will be compared to similar studies on injection of bone marrow mononuclear cells. We will use both anatomical and electrophysiological techniques to study the functional recovery of the remyelinated axons. We will also use a second lesion model system (a myelin-deficient mouse, shiverer) to determine if myelin repair by systemic bone marrow delivery can be achieved in a naturally occurring model of dysmyelination where gliosis is present. Many of the myelin profiles observed subsequent to bone marrow transplantation are characteristic of peripheral myelin. We will distinguish central from peripheral myelin. Completion of these studies should allow us to better understand the potential of MSCs to repair myelin. While these approaches are experimental in animal models, the prospect of using an expandable and renewable source of cells from bone marrow to repair the demyelinated CNS by systemic delivery has implications for future consideration of such an approach in man. ? ?
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