Chemical Engineering Department, Northwestern University, Evanston, IL, 60208-3120, U.S.A.
Cytotechnology. 1998 Nov;28(1-3):213-27. doi: 10.1023/A:1008010605287.
CO2 partial pressure (pCO2) in industrial cell culture reactors may reach 150-200 mm Hg, which can significantly inhibit cell growth and recombinant protein production. Due to equilibrium with bicarbonate, increased pCO2 at constant pH results in a proportional increase in osmolality. Hybridoma AB2-143.2 cell growth rate decreased with increasing pCO2 in well-plate culture, with a 45% decrease at 195 mm Hg with partial osmolality compensation (to 361 mOsm kg- 1). Inhibition was more extensive without osmolality compensation, with a 63% decrease in growth rate at 195 mm Hg and 415 mOsm kg-1. Also, the hybridoma death rate increased with increasing pCO2, with 31- and 64-fold increases at 250 mm Hg pCO2 for 401 and 469 mOsm kg- 1, respectively. The specific glucose consumption and lactate production rates were 40-50% lower at 140 mm Hg pCO2. However, there was little further inhibition of glycolysis at higher pCO2. The specific antibody production rate was not significantly affected by pCO2 or osmolality within the range tested. Hybridomas were also exposed to elevated pCO2 in continuous culture. The viable cell density decreased by 25-40% at 140 mm Hg. In contrast to the well-plate cultures, the death rate was lower at the new steady state at 140 mm Hg. This was probably due to higher residual nutrient and lower byproduct levels at the lower cell density (at the same dilution rate), and was associated with increased cell-specific glucose and oxygen uptake. Thus, the apparent effects of pCO2 may vary with the culture system.
CO2 分压（pCO2）在工业细胞培养反应器中可能达到 150-200 毫米汞柱，这会显著抑制细胞生长和重组蛋白的生产。由于与碳酸氢盐的平衡，在恒定 pH 值下增加的 pCO2 会导致渗透压成比例增加。在微孔板培养中，杂交瘤 AB2-143.2 细胞的生长速率随 pCO2 的增加而降低，在 195 毫米汞柱时部分渗透压补偿（至 361 毫渗透压千克-1）时降低了 45%。在没有渗透压补偿的情况下，抑制作用更为广泛，在 195 毫米汞柱和 415 毫渗透压千克-1 时，生长速率降低了 63%。此外，杂交瘤死亡率随 pCO2 的增加而增加，在 250 毫米汞柱 pCO2 时分别增加了 31 倍和 64 倍，分别为 401 和 469 毫渗透压千克-1。在 140 毫米汞柱 pCO2 时，特定的葡萄糖消耗和乳酸产生速率降低了 40-50%。然而，在更高的 pCO2 下，糖酵解的抑制作用很小。在测试范围内，特定的抗体产生速率不受 pCO2 或渗透压的影响。杂交瘤也在连续培养中暴露于升高的 pCO2。在 140 毫米汞柱时，活细胞密度降低了 25-40%。与微孔板培养相比，在新的稳定状态下，140 毫米汞柱时的死亡率较低。这可能是由于在较低的细胞密度下（在相同的稀释率下）残留营养物质和副产物水平较高，并且与细胞特异性葡萄糖和氧气摄取增加有关。因此，pCO2 的明显影响可能因培养系统而异。
