HEPATOCYTE CULTURE ON BIODEGRADABLE POLYMERIC SUBSTRATES

HEPATOCYTE CULTURE ON BIODEGRADABLE POLYMERIC SUBSTRATES
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DOI:
10.1002/bit.260380207
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发表时间:
1991-06-20
影响因子:
3.8
通讯作者:
LANGER, R
LANGER, R
中科院分区:
工程技术2区
文献类型:
--
作者:
CIMA, LG;INGBER, DE;LANGER, R

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在体外研究了大鼠肝细胞与可生物降解聚合物基质的相互作用,以评估聚合物材料用于细胞移植装置的适用性。通过与基质包被或胶原包被聚苯乙烯培养皿两种对照基质进行比较,研究了细胞粘附动力学、细胞生长和维持细胞生化功能的动力学,这些膜由聚(D, l -乳酸-羟基乙酸,88:12)(PLGA)或聚(l -乳酸)和聚(l -乳酸)(PLLA)的50/50 (w/w)混合物形成。细胞对两种聚合物底物的粘附率与胶原对照底物的粘附率相似,但在两种聚合物中,只有混合物适合延长培养。维持在聚合物混合膜上的肝细胞显示了通过白蛋白分泌率测量的分化细胞功能的保留-膜上细胞的白蛋白分泌率与基质上细胞的白蛋白分泌率相同,并且达到了报道的体内水平范围(140-160 μ g/10(6)个细胞/24小时)。相比之下,维持在胶原包被聚苯乙烯培养皿上的肝细胞的白蛋白分泌在5天后下降到初始水平的三分之一,第5天维持在聚合物混合膜上的细胞的五分之一。肝细胞在培养过程中对分化细胞功能的这种保留,以前只在肝细胞在外源性细胞外基质蛋白存在下培养或与另一种细胞类型共培养时观察到。除了保持分化功能外,维持在聚合物混合膜上的细胞也显示出与维持在胶原包被聚苯乙烯(一种最适合DNA合成的底物)上的对照组相似的DNA合成率。
The interactions of primary rat liver cells with biodegradable polymeric substrates were investigated in vitro to assess the suitability of the polymer materials for use in cell transplantation devices. The kinetics of cell adhesion to, and the growth and biochemical function of cells maintained on, films formed from poly (D,L-lactic-co-glycolic acid, 88:12) (PLGA) or from a 50/50 (w/w) blend of PLGA and poly (L-lactic acid) (PLLA) were evaluated in comparison to two control substrates, matrigel coated or collagen-coated polystyrene petri dishes. The rate of cell adhesion to both types of polymeric substrates was similar to the rate of adhesion to the collagen control substrate, but of the two polymers, only the blend was suitable for extended culture. Hepatocytes maintained on the polymer blend films showed retention of differentiated cell function as measured by the rate of albumin secretion-the rate of albumin secretion by cells on the films was the same as the rate for cells on matrigel and reached a level in the range of reported in vivo levels (140-160-mu-g/10(6) cells/24 h). In contrast, albumin secretion by hepatocytes maintained on collagen-coated polystyrene culture dishes declined over five days to a level one third that of the initial level and one fifth that of cells maintained on the polymer blend films on day five. Such retention of differentiated cell function by hepatocytes in culture has previously been observed only when hepatocytes were cultured in the presence of exogenous extracellular matrix proteins or were cocultured with another cell type. In addition to retention of differentiated function, the cells maintained on the polymer blend films also displayed rates of DNA synthesis similar to controls maintained on collagen-coated polystyrene, a substrate optimal for DNA synthesis.