Genetic modification of human embryonic stem cells with adenoviral vectors: differences of infectability between lines and correlation of infectability with expression of the coxsackie and adenovirus receptor.
Adenovirus is an efficient vector for expression of transgenes in dividing and nondividing cells. However, very few studies of human embryonic stem cells (hESCs) have utilized adenoviral vectors. We examine here the ability of adenovirus to infect naive hESCs and the differentiated derivatives of multiple hESC lines. We found a striking variation in adenovirus infection rates between lines. The variability in infection rates was positively correlated with the expression of the coxsackievirus and adenovirus receptor, but not that of alpha(nu)-integrin. Adenoviral infection did not interfere with the expression of pluripotency markers, even after passaging. In addition, infection did not affect differentiation of hESC-derived neural precursors in vitro. We also found that green fluorescent protein expression mediated by adenovirus can be a useful marker for tracking hESC in xenografts. We conclude that adenovirus is a practical vector for genetic modification of naive hESC from most, but not all lines, but may be more generally useful for gene transfer into differentiated derivatives of hESC lines.
Brokhman
Irina
I
Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
Pomp
Oz
O
Fishman
Lital
L
Tennenbaum
Tamar
T
Amit
Michal
M
Itzkovitz-Eldor
Joseph
J
Goldstein
Ronald S
RS
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002642:Chick Embryo; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
D015415:Biomarkers; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D039564:Integrin alphaV; D011991:Receptors, Virus