Functional Repair of Rat Corticospinal Tract Lesions Does Not Require Permanent Survival of an Immunoincompatible Transplant

Abstract

Cell transplantation is one of the most promising strategies for repair of human spinal cord injuries. Animal studies from a number of laboratories have shown that transplantation of olfactory ensheathing cells cultured from biopsies of the olfactory bulb mediate axonal regeneration and remyelination and restore lost functions in spinal cord injuries. For translation from small laboratory experimental injuries to the large spinal cord injuries encountered in human patients the numbers of cells that can be obtained from a patient's own olfactory bulb becomes a serious limiting factor. Furthermore, removal of an olfactory bulb requires invasive surgery and risks unilateral anosmia. We here report that xenografted mouse bulbar olfactory ensheathing cells immunoprotected by daily cyclosporine restore directed forepaw reaching function in rats with chronic C1/2 unilateral corticospinal tract lesions. Once function had been established for 10 days, cyclosporine was withdrawn. Thirteen out of 13 rats continued to increase directed forepaw reaching. Immunohistochemistry shows that in all cases neurofilament-positive axons were present in the lesion, but that the grafted cells had been totally rejected. This implies that once grafted cells have acted as bridges for axon regeneration across the lesion site their continued presence is no longer necessary for maintaining the restored function. This raises the possibility that in the future a protocol of temporary immunoprotection might allow for the use of the larger available numbers of immunoincompatible allografted cells or cell lines, which would avoid the need for removing a patient's olfactory bulb.