Viability of HEMA-MMA microencapsulated model hepatoma cells in rats and the host response

Viability of HEMA-MMA microencapsulated model hepatoma cells in rats and the host response
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DOI:
10.1089/107632700320784
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发表时间:
2000-04-01
期刊:
影响因子:
--
通讯作者:
Sefton, MV
Sefton, MV
中科院分区:
生物2区
文献类型:
--
作者:
Babensee, JE;Sefton, MV

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小直径甲基丙烯酸羟乙酯-甲基丙烯酸甲酯(HER HEMA-MMA;75% HEMA)微胶囊含有活的大鼠肝癌 H4IIEC3 细胞的聚集体,在植入 Wistar 大鼠的网膜袋后,在 7 天但不是 14 天时含有活细胞。对人肝癌 HepG2 细胞的微囊聚集体进行类似的移植,即使在 7 天后也没有产生活细胞。活力的丧失归因于组织反应,因为两种封装的细胞类型在体外仍然具有活力。然而,尚不清楚细胞是否在体内失去活力,导致侵袭性组织反应,或者后者是否导致细胞饥饿或死亡。第一天时,含有大鼠或人肝癌细胞的微胶囊的组织反应是一层细胞厚且无血管。后来,组织反应由三个区域组成:巨噬细胞、成纤维细胞和一些附着在聚合物膜上的异物巨细胞、成纤维细胞和胶原的致密区域以及血管化肉芽组织区域。 4 天后,组织反应迅速发生血管化,并维持长达 14 天。即使在第 14 天,也观察到了免疫细胞,这表明对从封装细胞中脱落的抗原有持续的免疫反应。
Small diameter hydroxyethyl methacrylate-methyl methacrylate (HER HEMA-MMA; 75% HEMA) microcapsules containing an aggregate of viable rat hepatoma H4IIEC3 cells, after implantation into an omental pouch in Wistar rats, contained viable cells at 7 days but not 14 days. A similar transplantation of microencapsulated aggregates of human hepatoma HepG2 cells did not result in viable cells even at 7 days. The loss of viability was attributed to the tissue reaction, because both encapsulated cell types remained viable in vitro. However, it is not clear if the cells lost their viability in vivo, leading to the aggressive tissue reaction or if the latter caused the cells to starve or otherwise die. The tissue reactions to microcapsules containing rat or human hepatoma cells at day 1 was one cell layer thick and avascular. At later times, tissue reactions were comprised of three regions: macrophages, fibroblasts, and some foreign body giant cells apposed to the polymer membrane, a dense region of fibroblasts and collagen, and a region of vascularized granulation tissue. Prompt vascularization of the tissue reactions occurred after 4 days and was maintained for up to 14 days. Even at 14 days, immune cells were observed, suggesting a continued immune response toward antigens shed from the encapsulated cells.