A pure culture of oligodendrocytes has been developed starting from brain hemispheres of newborn rats. Various effects of acidic and basic fibroblast growth factors (FGFs) on the development of oligodendrocytes have been examined and compared. Both factors elicited similar effects, i.e. stimulation of the proliferation, inhibition of the specific activity of the marker enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase and decrease of the ratio of myelin basic protein positive cells. These results indicate that FGFs are very potent mitogens for oligodendrocytes, even in the absence of other cell types, but that they elicit a negative effect on the cell maturation, possibly related to their strong effect on proliferation.

Ad CFTR, a replication-deficient adenovirus expressing the human cystic fibrosis transmembrane conductance regulator (CFTR), was administered by aerosolization in a single escalating dose to three pairs (cohorts) of cystic fibrosis (CF) patients. Buffer only was administered to the nose and lungs 9-14 days before nasal instillation of virus followed the day after by aerosolization of Ad CFTR to the lung. Nasal doses (defined in terms of viral plaque forming units, pfu) were 10(5), 10(7), and 4 x 10(8), whereas aerosolized doses were 10(7), 10(8), 5.4 x 10(8) for each cohort, respectively. No acute toxic effects were observed in the first 4 weeks after virus treatment. Shedding of infectious Ad CFTR was never detected, whereas detection of vector DNA sequences and CFTR expression demonstrated DNA transfer to the nose and airways of patients. No significant deviations in immunological and inflammatory parameters were observed in serum and in bronchoalveolar lavage (BAL). Importantly, for all patients, the serum anti-adenovirus antibody levels did not change significantly from baseline and no antibodies against adenovirus were found in BAL.

Astroblasts from brain of newborn rat can survive and even proliferate to some extent in a chemically defined medium containing no other growth factor than insulin, providing they are grown first in the presence of fetal calf serum for at least 4 days (Weibel et al., 1984, Int. J. devl Neurosci. 2, 355-366). We found that thrombin is a potent mitogen for these cells, in vitro. The mitogenic activity of thrombin for astroblasts can be compared to that of the astroglial growth factor on astroblasts. However, in contrast to the bFGF, thrombin does not modify significantly the morphology of the cells and their synthesis of glutamine synthetase, an astroglial marker in rat brain. Some other proteases are also able to stimulate the proliferation of astroblasts, but to a lesser extent than thrombin. Thrombin does not stimulate the proliferation of oligodendroblasts from newborn rat and of neuroblasts from 13-day-old rat embryo. These results suggest that in the central nervous system thrombin might play a role in the induction of astrocyte proliferation after brain injury.

The two fibroblast growth factors called acidic and basic FGF (aFGF and bFGF) show a strong homology (55%) of their amino acid sequence (Esch et al.: Proc. Nat. Acad. Sci. USA 85:6507-6511, 1985). The effects of these factors on the rate of proliferation of rat astroblasts and on the expression of glutamine synthetase activity in cells grown in primary culture were investigated and compared under various culture conditions. In all the experimental conditions used, both growth factors triggered the proliferation of the cells to the same extent and with similar dose dependence. The mitogenic activities of aFGF and bFGF were potentiated similarly by heparan sulfate and by heparin, with a maximum stimulation of about 100% at 100 micrograms/ml heparin. Treatment of the cells with either of the two factors resulted in identical enhancement of the activity of glutamine synthetase relative to total proteins. These results suggest that both factors act either through the same membrane receptors or through different receptors that mediate nearly identical effects.