Remyelination of the non-human primate CNS axons by transplantation of porcine olfactory ensheathing cells

Usually there is no regeneration in the central nervous system. Only exception is the olfactory system in which regeneration can be found throughout lifetime and responsible for this phenomenon to enhance regeneration in the CNS are cells which ensheath the axons: the olfactory ensheathing glia cells (OECs). In addition to the regeneration, OECs, which usually do not produce myelin in their original position, start to remyelinate demyelinated axons after transplantation in such a lesion. Taken all these together they are promising candidates in axonal injuries. Autologous OECs could in principle derive from biopsy, harvesting sufficient numbers remains problematic. Xenotransplantation provides another potential source for OECs for cell based transplantation therapies. In prospect of the clinical use, the repair potential of OECs in the primate model has to be determined. OECs were derived from transgenic pigs expressing human alpha-1,2-fucosyltransferase (H-transferase). By using a human monoclonal p75 antibody, the purity of the primary culture was determined. African green monkey spinal cord axons were demyelinated by microinjection of ethidium bromide into the dorsal funiculus and OECs were transplanted into the demyelinated lesion. FACS analysis determined H-epitope expression on the OEC surface. After transplantation, immunohistochemistry revealed p75 NGF receptor expression in the regions of remyelination. Four weeks post-transplantation of OECs, robust remyelination was found in 62.5% of the lesion sites. In vitro assays demonstrated that (a) the applied cell suspension consisted of more than 98% OECs, (b) the majority of the cells expressed the transgene, and (c) expression of the H-transferase gene reduced complement activation more than 2-fold compared to the non-transgenic control. These data demonstrate that xenotransplantation of characterised OECs from pigs engineered to express the H-epitope into the primate spinal cord axons results in extensive remyelination. This is the first demonstration of remyelination in the central nervous system in a non-human primate model.