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Integration of genetically modified adult astrocytes into the lesioned rat spinal cord
Author(s) -
Pencalet Philippe,
Serguera Che,
Corti Olga,
Privat Alain,
Mallet Jacques,
Giménez y Ribotta Minerva
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20697
Subject(s) - spinal cord , glial fibrillary acidic protein , astrocyte , transplantation , green fluorescent protein , spinal cord injury , transgene , biology , viral vector , pathology , ex vivo , central nervous system , medicine , immunohistochemistry , immunology , neuroscience , in vivo , surgery , recombinant dna , gene , biochemistry , microbiology and biotechnology
Combination of ex vivo gene transfer and cell transplantation is now considered as a potentially useful strategy for the treatment of spinal cord injury. In a perspective of clinical application, autologous transplantation could be an option of choice. We analyzed the fate of adult rat cortical astrocytes genetically engineered with a lentiviral vector transplanted into a lesioned rat spinal cord. Cultures of adult rat cortical astrocytes were infected with an HIV‐1–derived vector (TRIP‐CMV‐GFP) and labeled with the fluorescent dye Hoechst. Transfected and labeled astrocyte suspension was injected at T11 in rats in which spinal cord transection at T7–T8 levels had been carried out 1 week earlier. Six weeks after grafting, the animals were sacrificed and transplants were retrieved either by Hoechst fluorescence or by immunohistochemistry for detection of glial fibrillary acidic protein (GFAP) and vimentin. Grafted astrocytes expressing green fluorescent protein (GFP) were found both at the injection and transection sites. Genetically modified astrocytes thus survived, integrated, and migrated within the host parenchyma when grafted into the completely transected rat spinal cord. In addition, they retained some ability to express the GFP transgene for at least 6 weeks after transplantation. Adult astrocytes infected with lentiviral vectors can therefore be a valuable tool for the delivery of therapeutic factors into the lesioned spinal cord. © 2005 Wiley‐Liss, Inc.