Remyelination of the nonhuman primate spinal cord by transplantation of H-transferase transgenic adult pig olfactory ensheathing cells.
Olfactory ensheathing cells (OECs) have been shown to mediate remyelination and to stimulate axonal regeneration in a number of in vivo rodent spinal cord studies. However, whether OECs display similar properties in the primate model has not been tested so far. In the present study, we thus transplanted highly-purified OECs isolated from transgenic pigs expressing the alpha1,2 fucosyltransferase gene (H-transferase or HT) gene into a demyelinated lesion of the African green monkey spinal cord. Four weeks posttransplantation, robust remyelination was found in 62.5% of the lesion sites, whereas there was virtually no remyelination in the nontransplanted controls. This together with the immunohistochemical demonstration of the grafted cells within the lesioned area confirmed that remyelination was indeed achieved by OECs. Additional in vitro assays demonstrated 1) that the applied cell suspension consisted of >98% OECs, 2) that the majority of the cells expressed the transgene, and 3) that expression of the HT gene reduced complement activation more than twofold compared with the nontransgenic control. This is the first demonstration that xenotransplantation of characterized OECs into the primate spinal cord results in remyelination.
Radtke
Christine
C
Department of Neurology, Yale University School of Medicine, New Haven, an Neuroscience Research Center, VA Medical Center, West Haven, Connecticut 06516, USA.
Akiyama
Yukinori
Y
Brokaw
Jane
J
Lankford
Karen L
KL
Wewetzer
Konstantin
K
Fodor
William L
WL
Kocsis
Jeffery D
JD
D000818:Animals; D030801:Animals, Genetically Modified; D016380:Brain Tissue Transplantation; D050260:Carbohydrate Metabolism; D017690:Cell Transplantation; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D000882:Haplorhini; D009186:Myelin Sheath / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000637:transplantation*; D012038:Regeneration; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D014183:Transplantation, Heterologous
D003165:Complement System Proteins; D005647:Fucosyltransferases