Animal cells from endocrine glands have potential applications in biop
rocessing, for the production of hormones, enzymes, possibly also reco
mbinant proteins, and in tissue engineering, for the development of im
munoisolated, implantable devices for long-term treatment of endocrine
disorders. Immunoisolation can be achieved by surrounding cells with
a biocompatible polymer which allows diffusion of nutrients and metabo
lites, including hormones, but excludes higher molecular weight antibo
dies and cytotoxic cells. Primary hormone-secreting cells cannot be ef
fectively amplified in culture, so the large-scale application of impl
antable systems based on such cells is limited by cell availability. I
n this study, we conducted an initial assessment of the feasibility of
using transformed, continuous cell lines in immunoisolated devices. T
he model system employed consisted of mouse pituitary tumor AtT-20 cel
ls which secrete recombinant proinsulin and an insulin-like peptide an
d exhibit a high growth potential. Cells were cultivated as spheroids
in spinner flasks and entrapped as such in alginate/polylysine/alginat
e beads. Free and entrapped spheroids were propagated in fed-batch, su
spension cultures. Entrapment did not significantly affect spheroid me
tabolism or basal secretion. Entrapped spheroids did not increase in s
ize or number and maintained roughly constant metabolic and basal secr
etory activities over a 15-day period. Free spheroids in suspension in
creased in size during the same period, but also maintained constant m
etabolism and basal secretion, apparently because of a concomitant inc
rease in hypoxic and/or necrotic cells. The potential of using continu
ous cell lines in the development of bioartificial endocrine organs is
discussed.