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Adenovirus‐mediated suicide gene therapy in an in vitro model of reactive gliosis
Author(s) -
Audouy Sandrine,
Mallet Jacques,
Privat Alain,
Ribotta Minerva Giménez Y
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(19990201)25:3<293::aid-glia9>3.0.co;2-g
Subject(s) - suicide gene , biology , thymidine kinase , astrogliosis , genetic enhancement , viral vector , transfection , ganciclovir , gliosis , in vivo , cell culture , cancer research , herpes simplex virus , virology , microbiology and biotechnology , gene , central nervous system , virus , recombinant dna , neuroscience , human cytomegalovirus , genetics
Adenovirus‐mediated herpes simplex thymidine kinase/ganciclovir (HSV‐tk/GCV) system has been demonstrated to be efficient for the treatment of experimental brain tumors. However, no study has been directed to the elimination of proliferating cellular populations in other pathological conditions. In this study we used this suicide gene approach in a primary culture of astrocytes, as a model of reactive gliosis, in order to evaluate its efficiency as a therapeutic strategy for post‐traumatic astrogliosis in vivo . First, we evaluated the peak of astrocytic proliferation to characterize our model. Second, the efficiency of adenovirus‐mediated lac Z gene transfer is shown to be dependent on vector multiplicity of infection (MOI). As expected, the cells transfected with the HSV‐tk gene showed an increase in sensibility to GCV compared with cells transfected with lac Z gene. Finally, an unexpected interaction between the adenoviral vector and bromodeoxyuridine (BrdU) or [ 3 H]‐Thymidine ([ 3 H]‐Thy) was evidenced in transfected cultures, whose interpretation is discussed. The present study demonstrates that a recombinant adenoviral vector carrying the tk gene confers to in vitro cultured astrocytes a cytotoxic sensibility to GCV, and that this system constitutes a potentially efficient tool to eliminate the hyperplasia of astrocytes following injury to the central nervous system in vivo. GLIA 25:293–303, 1999. © 1999 Wiley‐Liss, Inc.