New miniaturized hollow-fiber bioreactor for in vivo like cell culture, cell expansion, and production of cell-derived products.
We have developed a miniaturized hollow-fiber bioreactor system for mammalian cell culture with a volume of 1 mL. Cell and medium compartments of the bioreactor are separated by a semipermeable membrane, and oxygenation of the cell compartment is accomplished using an oxygenation membrane. As a result of the geometry of the transparent housing, cells can be observed by microscopy during culture. The leukemic cell lines CCRF-CEM, HL-60, and REH were cultivated up to densities of 3.5 x 10(7)/mL without medium change or manipulation of the cells. As shown using CCRF-CEM cells, growth in the bioreactor was strongly influenced and could be controlled by the medium flow rate. As a consequence, consumption of glucose and generation of lactate varied with flow rate. Depending on the molecular size cutoff of the membranes used, added growth factors such as GM-CSF, as well as factors secreted from the cells, are retained in the cell compartment for up to 1 week. This new miniaturized hollow-fiber bioreactor offers advantages in tissue engineering by continuous nutrient supply for cells in high density, retention of added or autocrine produced factors, and undisturbed long-term culture in a closed system.
Gloeckner
H
H
Acordis Research, Obernburg, Germany.
Lemke
H D
HD
D000818:Animals; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002455:Cell Division; D003470:Culture Media / Q000493:pharmacokinetics; D015194:Diffusion Chambers, Culture / Q000295:instrumentation / Q000379:methods; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006801:Humans; D008904:Miniaturization; D010107:Oxygenators, Membrane; D014407:Tumor Cells, Cultured / Q000378:metabolism
D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor