The effects of
alginate composition on cell growth as well as the metabolic and secretory profile of transformed beta-cells entrapped in
alginate/poly-L-lysine/
alginate (APA) solid beads were investigated following entrapment of beta TC3 mouse
insulinoma cells in
alginate composed of either high
mannuronic acid or high
guluronic acid residues. Entrapped cultures were maintained in spinner flasks for 40-60 days. The pattern of cell growth and the overall rates of
glucose consumption and insulin secretion were investigated. Cultures of beta TC3 cells entrapped in
alginate composed predominantly of
mannuronic acid units (77%) displayed a linear increase in the rates of
glucose consumption and insulin secretion concomitant with an increase in cell population in the periphery of the beads. Conversely, cultures of beta TC3 cells entrapped in
alginate composed predominantly of high
guluronic acid units (69%) displayed a decrease in the rates of
glucose consumption and insulin secretion during the first three weeks of culture, followed by a rapid recovery that surpassed the initial rates by day 40. This biphasic pattern was concomitant to a decrease in viable cells during the first three weeks as ascertained by histology, followed by an increase in cell proliferation. Cell growth in high
guluronic acid alginate took place at random locations throughout the solid bead and not in the periphery, as was the case in high
mannuronic acid alginate preparations. Possible reasons for these differences and the significance of these findings in the context of a bioartificial pancreas composed of APA entrapped transformed cells are discussed.