Efficient myelin repair in the macaque spinal cord by autologous grafts of Schwann cells

• Published in: Brain (London, England : 1878) England : 1878), 2005-03, Vol.128 (3), p.540-549
• Main Authors: Bachelin, Corinne, Lachapelle, François, Girard, Christelle, Moissonnier, Pierre, Serguera-Lagache, Che, Mallet, Jacques, Fontaine, Denys, Chojnowski, Alexandre, Le Guern, Eric, Nait-Oumesmar, Brahim, Baron-Van Evercooren, Anne
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Differentiation; Cell Division; Cells, Cultured; CNS; Demyelinating Diseases - pathology; Demyelinating Diseases - therapy; Disease Models, Animal; Female; GalC = galactocerebroside; Genetic Vectors; GFP = green fluorescent protein; HIV - genetics; hrNDFβ = human recombinant neu differentiation factor β; IGF I = insulin-like growth factor 1; Injuries of the nervous system and the skull. Diseases due to physical agents; Macaca; Macaca fascicularis; Male; Medical sciences; Mice; Mice, Nude; Myelin Sheath - physiology; Myelin Sheath - ultrastructure; Nerve Regeneration; Neurology; Neurosurgery; P0 = protein 0; PGK = phosphoglycerate kinase; primate; remyelination; SC = Schwann cells; Schwann cell; Schwann Cells - transplantation; Schwann Cells - virology; Skull, brain, vascular surgery; Spinal Cord - ultrastructure; Spinal Cord Diseases - pathology; Spinal Cord Diseases - therapy; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Transduction, Genetic; Traumas. Diseases due to physical agents
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awh406

Experimental transplantation in rodent models of CNS demyelination has led to the idea that Schwann cells may be candidates for cell therapy in human myelin diseases. Here we investigated the ability of Schwann cells autografts to generate myelin in the demyelinated monkey spinal cord. We report that monkey Schwann cells derived from adult peripheral nerve biopsies retain, after growth factor expansion and transduction with a lentiviral vector encoding green fluorescent protein, the ability to differentiate in vitro into promyelinating cells. When transplanted in the demyelinated nude mouse spinal cord, they promoted functional and anatomical repair of the lesions (n = 12). Furthermore, we obtained evidence by immunohistochemistry (n = 2) and electron microscopy (n = 4) that autologous transplantation of expanded monkey Schwann cells in acute lesions of the monkey spinal cord results in the repair of large areas of demyelination; up to 55% of the axons were remyelinated by donor Schwann cells, the remaining ones being remyelinated by oligodendrocytes. Autologous grafts of Schwann cells may thus be of therapeutic value for myelin repair in the adult CNS.