Microfabricated Biocapsules Provide Short-Term Immunoisolation of Insulinoma Xenografts

Microfabricated Biocapsules Provide Short-Term Immunoisolation of Insulinoma Xenografts
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DOI:
10.1023/a:1009948524686
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发表时间:
1999-06-01
影响因子:
2.8
通讯作者:
Ferrari, Mauro
Ferrari, Mauro
中科院分区:
工程技术3区
文献类型:
--
作者:
Desai, Tejal A.;Chu, Wen Hwa;Ferrari, Mauro

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本研究检测了两种胰岛素瘤细胞系RIN(1048)和β TC6F7在微制造生物胶囊内的生存能力和功能。在生物胶囊的制造过程中集成了表面和体微加工,形成了孔径分布均匀、机械和化学稳定性良好的扩散膜,并被各向异性蚀刻的硅片包围,硅片作为封装腔。胰岛素瘤细胞(4500个细胞/生物胶囊)被包裹在这些微制造的生物胶囊中,在BALB-C小鼠体内植入或体外孵育后进行静态孵育研究。对制备的微胶囊进行检测发现,孔径为18nm的微胶囊的RIN细胞胰岛素刺激指数约为1.5,bTC6F7细胞胰岛素刺激指数约为3.6,与体外培养的生物胶囊指数相似。体外和体内66nm生物胶囊的细胞刺激反应降低了80%,而18nm生物胶囊的细胞刺激反应降低了20%,这表明免疫隔离效果在很大程度上取决于在18nm或更小的尺寸范围内实现均匀的孔径。本研究证明了利用微制备生物胶囊对胰岛素瘤细胞系进行免疫分离的可行性。微制造的生物胶囊可以作为传统聚合物基生物胶囊的替代品,可能用作体内胰岛素分泌生物反应器。
This study examines the viability and functionality of two insulinoma cell lines, RIN (1048) and beta TC6F7, encapsulated within microfabricated biocapsules. Surface and bulk micromachining are integrated in the biocapsule fabrication process, resulting in a diffusion membrane with uniform pore size distribution as well as mechanical and chemical stability, surrounded by an anisotropically-etched silicon wafer, which serves as the encapsulation cavity. Insulinoma cells (4500 cells/biocapsule) were enclosed within these microfabricated biocapsules and subjected to a static incubation study after either implantation in BALB-C mice or incubation in vitro. Examination of retrieved microfabricated biocapsules revealed an insulin stimulatory index of approximately 1.5 for encapsulated RIN cells and 3.6 for encapsulated bTC6F7 cells for biocapsules with 18nm pore sized microfabricated membranes, similar to indices of biocapsules incubated in vitro. There was an 80% decrease in cell stimulatory response between in vitro and in vivo 66 nm-biocapsules as compared to 20% for 18 nm-biocapsules, indicating that the immunoisolatory effectiveness depends greatly on achieving uniform pore sizes in the size range of 18nm or smaller. The present study demonstrates the feasibility of using microfabricated biocapsules for the immunoisolation of insulinoma cells lines. The microfabricated biocapsule may serve as an alternative to conventional polymeric based biocapsules for possible use as in vivo insulin secreting bioreactor.