CHARACTERIZATION OF HEMATOPOIETIC-CELL EXPANSION, OXYGEN-UPTAKE, AND GLYCOLYSIS IN A CONTROLLED, STIRRED-TANK BIOREACTOR SYSTEM

Cultures of umbilical cord blood and mobilized peripheral blood mononu clear cells were carried out in a stirred bioreactor with pH and disso lved oxygen control. Expansion of total cells and colony-forming units granulocyte-macrophage was greatly enhanced by the use of a cell-dilu tion feeding protocol (as compared to a cell-retention feeding protoco l). The specific oxygen consumption rate (q(O2)) for these cultures ra nged from 1.7 x 10(-8) to 1.2 x 10(-7) mu mol/(cell.h). The maximum in q(O2) for each culture closely corresponded with the maximum percenta ge of progenitor or colony-forming cells (CFCs) present in the culture . The maximum q(O2) values are slightly less than those reported for h ybridomas, while the lowest q(O2) values are somewhat greater than tho se reported for mature granulocytes. Examination of the ratio of lacta te production to oxygen consumption in these cultures suggests that po st-progenitor cells of the granulomonocytic lineage obtain a greater p ortion of their energy from glycolysis than do CFCs. The different met abolic profiles of CFCs and more mature cells suggest that monitoring the uptake or production of oxygen, lactate, and other metabolites wil l allow estimation of the content of several cell types in culture.