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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 × 107/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.