Cultivation of Calcium-Alginate Encapsulated Myeloma Cells in a Bioreactor

Abstract

Hybridization partners of hybridoma cells which produce monoclonal antibodies (MAb) are myeloma cells.
Myeloma cells which are B-lymphoma cells can proliferate easily and be produced cheaply. This cell line shows many
characteristic similarities with hybridoma cells. When calcium alginate encapsulated hybridoma cells are cultivated in
bioreactors, the amount of MAb and viable cell number increase approximately 3-10 folds depending on the cell
concentration used. In this study, concentration, time and other factors were optimized for MAb production with a high
yield and quality. The toxicity of the Ca-alginate to the cells was determined. In order to optimize the conditions, different
concentrations of sodium alginate and calcium chloride were used to keep myeloma cells alive for 15-20 days in the
bioreactor. Under optimized conditions, Ag8 myeloma cells which were encapsulated in a 1 mm diameter beads were
cultivated in a stirred bioreactor with a working volume of 700 ml for ten days. Encapsulation of the cells was carried out
using 1.2% (w/v) Na-alginate (pH adjusted to 7.2) and 1.5% (w/v) CaCl2 (pH adjusted to 7.4) which was used as a
crosslinking agent. The pH of the medium, glucose consumption and lactic acid production were measured throughout the
cultivation with daily intervals. The results indicated that after 2 days of logarithmic phase the Ca-alginate encapsulated
myeloma cells stayed in stationary phase for about 6 days which was then followed by cell death.