Whikehart D R, Montgomery B, Wells J D
Department of Physiological Optics, School of Optometry, University of Alabama, Birmingham 35294.
Invest Ophthalmol Vis Sci. 1989 Feb;30(2):335-8.
As cells grown in tissue culture age, they typically become altered when compared to their in vivo counterparts. Bovine corneal endothelial cells were grown in culture for periods up to 60 days (primary = 10 days; secondary = 50 days). The plasma membrane enzymes: Na+K+ ATPase and Mg2+ ATPase were assayed for specific activity at selected intervals throughout the growth periods. In primary cultures, it was found that Na+K+ ATPase was quite low at 5 days (0.05 units), but increased fourfold at 10 days (0.22 units). By contrast, Mg2+ ATPase changed little over the same period. Tissue cultures grown secondarily had Na+K+ ATPase activity fall 0.3 units (0.52 to 0.22) for 35 days after a single trypsinization. After five trypsinizations over a 50-day period, the activity fell 0.23 units (0.33 to 0.10). The alterations in Mg2+ ATPase activity were more complex in secondary cultures. In the instance in which a single trypsinization was used, the activity fell 0.15 units at day 20, rose 0.12 units (above the starting value) at day 25, then returned to the initial level by day 35. When multiple trypsinizations were used, the activity fell 0.06 units by day 30, then remained stable for the duration. The data may be indicative of mechanisms such as receptor alteration, feedback inhibition and genetic instability when these cells are grown in culture.
随着在组织培养中生长的细胞老化,与体内的对应细胞相比,它们通常会发生变化。牛角膜内皮细胞在培养中生长长达60天(原代培养 = 10天;传代培养 = 50天)。在整个生长期间的选定时间间隔测定质膜酶:Na⁺K⁺ATP酶和Mg²⁺ATP酶的比活性。在原代培养中,发现Na⁺K⁺ATP酶在第5天相当低(0.05单位),但在第10天增加了四倍(0.22单位)。相比之下,Mg²⁺ATP酶在同一时期变化不大。单次胰蛋白酶消化后,传代培养的组织培养物在35天内Na⁺K⁺ATP酶活性下降0.3单位(从0.52降至0.22)。在50天内进行五次胰蛋白酶消化后,活性下降0.23单位(从0.33降至0.10)。传代培养中Mg²⁺ATP酶活性的变化更为复杂。在单次使用胰蛋白酶消化的情况下,活性在第20天下降0.15单位,在第25天上升0.12单位(高于起始值),然后在第35天恢复到初始水平。当使用多次胰蛋白酶消化时,活性在第30天下降0.06单位,然后在剩余时间内保持稳定。这些数据可能表明这些细胞在培养中生长时存在受体改变、反馈抑制和遗传不稳定性等机制。