Ex vivo infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord.
BACKGROUND
Genetically modified pseudorabies virus (Prv) proved suitable for the delivery of foreign genes to rodent embryonic neurons ex vivo and maintaining foreign gene expression after transplantation into spinal cord in our earlier study. The question arose of whether human embryonic neurons, which are known to be more resistant to Prv, could also be infected with a mutant Prv. Specifically, we investigated whether a mutant Prv with deleted ribonucleotide reductase and early protein 0 genes has the potential to deliver marker genes (gfp and beta-gal) into human embryonic spinal cord neurons and whether the infected neurons maintain expression after transplantation into adult mouse cord.


RESULTS
The results revealed that the mutant Prv effectively infected human embryonic spinal cord neurons ex vivo and the grafted cells exhibited reporter gene expression for several weeks. Grafting of infected human embryonic cells into the spinal cord of immunodeficient (rnu-/rnu-) mice resulted in the infection of some of the host neurons.


CONCLUSIONS
These results suggest that Prv is suitable for the delivery of foreign genes into transplantable human cells. This delivery method may offer a new approach to use genetically modified cells for grafting in animal models where spinal cord neuronal loss or axon degeneration occurs.
Department of Ophthalmology, Faculty of General Medicine, University of Szeged, Szeged, Hungary.
Gábor
G
Márton
Dóra
D
Tombácz
Judit S
JS
Tóth
András
A
Szabó
Zsolt
Z
Boldogköi
Adám
A
Dénes
Akos
A
Hornyák
Antal
A
Nógrádi
D000818:Animals; D005822:Genetic Vectors; D011558:Herpesvirus 1, Suid / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000637:transplantation* / Q000821:virology*; D013116:Spinal Cord / Q000166:cytology / Q000637:transplantation* / Q000821:virology*