New miniaturized hollow-fiber bioreactor for in vivo like cell culture, cell expansion, and production of cell-derived products
New miniaturized hollow-fiber bioreactor for in vivo like cell culture, cell expansion, and production of cell-derived products
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DOI：
10.1021/bp010069q
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发表时间：
2001-09-01
影响因子：
2.9
通讯作者：
Lemke, HD
中科院分区：
文献类型：
--
作者：
Gloeckner, H;Lemke, HD
我们已经开发了一种小型化的中空纤维生物反应器系统，用于哺乳动物细胞培养，体积为1 mL。生物反应器的细胞隔室和培养基隔室由半透膜分开，并且细胞隔室的氧合使用氧合膜完成。由于透明外壳的几何形状，在培养期间可以通过显微镜观察细胞。白血病细胞系CCRF-CEM、HL-60和REH培养至密度为3.5 x 10（7）/ mL，无需更换培养基或操作细胞。如使用CCRF-CEM细胞所示，生物反应器中的生长受到强烈影响，并且可以通过培养基流速控制。因此，葡萄糖的消耗和乳酸的产生随流速而变化。取决于所用膜的分子大小截止值，添加的生长因子如GM-CSF以及从细胞分泌的因子在细胞隔室中保留长达1周。这种新型的小型中空纤维生物反应器通过高密度的细胞连续营养供应、添加或自分泌产生的因子的保留以及在封闭系统中不受干扰的长期培养而在组织工程中提供优势。
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.