In any therapeutic approach to treating hypomyelinating or demyelinating disorders is that involves glial cells transplantation, the grafter cells must be able to assemble a myelin sheath within inflammatory and/or gliotic areas of the CNS and be able to migrate towards focal areas od demyelinations; e.g., the isolated plaques of a multiple sclerosis patient. The long-term objective is to demonstrate that olfactory ensheathing cells can be used as part of a therapeutic approach in the treatment of hypomyelinating and demyelinating disorders in humans. Ensheathing cells provide ensheathment for unmyelinated olfactory axons in vivo but can also assemble a myelin sheath around appropriately-sized PNS and CNS axons. The main reason why ensheathing cells are more appealing than other glial cells types for treating myelin disorders is because they possess such a flexible phenotype, which enables them to become more astrocyte-like or more Schwann cell-like as dictated by the cellular milieu in which they reside. A fluorescent activated cell sorter could be used to obtain purified populations of ensheathing cells from an autologous nasal mucosal biopsy, which can be expanded in culture to increase the cell yield or to genetically modify them to further enhance their myelinating abilities. To meet these long-term objective, the PI proposes to determine whether the grafted cells: a) give rise to myelinating as well as non-myelinating cells as the need arises; b) integrate into areas of CNS injury (demyelinating, gliosis or inflammation) and into adjacent undamaged CNS tissue; c) migrate towards focal areas of inflammation or demyelination, an ability that would greatly improve the prospects of repairing multiple dispersed myelin lesions such as occurs in multiple sclerosis; and d) survive an inflammatory attack directed towards the CNS microenvironment into which they have been transplanted. In summary, the PI expects to show that ensheathing cells would be a definite asset to any therapeutic approach designed to treat hypomyelinating or demyelinating disorders to humans.
