Cell adhesion molecules in gene and cell therapy approaches for nervous system repair.

The inability of the central nervous system (CNS) to efficiently repair damages results in severe functional impairment after trauma or neurodegenerative/demyelinating diseases. Regeneration failure is attributed to inhibitory molecules creating a nonpermissive environment for axonal regrowth, and dictates the necessity for the development of novel therapeutic strategies. An emerging approach for improving regeneration is the use of gene therapy to manipulate cell adhesion molecule expression in experimental animal models of degeneration. Alternatively, cell transplantation to replace lost neurons and the grafting of myelinating cells to repair demyelinating lesions are promising approaches for treating CNS injuries and demyelination. Schwann cells (SCs), oligodendrocyte progenitors, olfactory ensheathing cells and embryonic and neural stem cells have been shown to form myelin after transplantation into the demyelinated CNS. The repair capacity of the peripheral nervous system (PNS) is much higher, but there is still a limit to the amount of nerve loss that can be bridged after injury, and longer nerve gaps call for the use of conduits populated with living cells. In both cases, the interaction of grafted cells with the host environment is of paramount importance for the incorporation and functional integration of these cells and the manipulation of cell adhesion molecules is an attractive approach towards achieving this goal. In this review we summarize data from the recent literature regarding the manipulation of cell adhesion molecule expression towards CNS and PNS repair and discuss the prospects for future therapeutic applications.