Adenovirus-mediated gene transfer of basic fibroblast growth factor promotes the survival of primary-cultured rat neuronal cells

We constructed two replication-deficient recombinant adenovirus vectors cod ing human basic fibroblast growth factor (bFGF), one with and one without t he interleukin-2 (IL-2) secretory signal sequence and examined their neurot rophic effects on primary neuronal cells in vitro. The primary neuronal cel ls were successfully infected at a high efficiency with the adenovirus vect ors, bFGF protein was detected in the culture medium of the neurons infecte d with both these vectors. The cells infected with the bFGF-expressing aden ovirus containing the IL-2 signal sequence showed 2- to 10-fold higher leve ls of secretion levels than cells infected with the native bFGF-expressing adenovirus alone. Both bFGF-expressing vectors augmented the survival of pr imary neuronal cells in an in vitro culture, compared with a mock infection or control virus infection. Notably, the cells infected with the bFGF-expr essing adenovirus containing the IL-2 signal sequence were markedly enhance d cell survival in the early phase of the culture, compared with the contro l cells and even those infected with the bFGF-expressing adenovirus without the IL-2 signal sequence. However, in the late phase of neuronal culture, neither viral vector could support the cell survival. In contrast the co-in fection of the bFGF-expressing vector with a Bcl-xL-expressing vector was e xtremely effective on neuronal survival. NeuroReport 11:2001-2006 (C) 2000 Lippincott Williams & Wilkins.