Desai T A, Chu W H, Rasi G, Sinibaldi-Vallebona P, Guarino E, Ferrari M
Department of Bioengineering, University of Illinois, Chicago 60607, USA.
Biomed Microdevices. 1999;1(2):131-8. doi: 10.1023/A:1009948524686.
This study examines the viability and functionality of two insulinoma cell lines, RIN (1048) and betaTC6F7, 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 betaTC6F7 cells for biocapsules with 18 nm 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 18 nm 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.
本研究考察了封装在微制造生物胶囊中的两种胰岛素瘤细胞系RIN(1048)和betaTC6F7的活力与功能。在生物胶囊制造过程中整合了表面微加工和体微加工，形成了一个孔径分布均匀且具有机械和化学稳定性的扩散膜，该扩散膜被用作封装腔的各向异性蚀刻硅片包围。将胰岛素瘤细胞(4500个细胞/生物胶囊)封装在这些微制造生物胶囊中，在植入BALB-C小鼠体内或体外培养后进行静态培养研究。对回收的微制造生物胶囊进行检测发现，对于具有18nm孔径微制造膜的生物胶囊，封装的RIN细胞的胰岛素刺激指数约为1.5，封装的betaTC6F7细胞的胰岛素刺激指数约为3.6，这与体外培养的生物胶囊的指数相似。与18nm生物胶囊的20%相比，体外和体内66nm生物胶囊之间的细胞刺激反应降低了80%，这表明免疫隔离效果在很大程度上取决于在18nm或更小尺寸范围内实现均匀孔径。本研究证明了使用微制造生物胶囊对胰岛素瘤细胞系进行免疫隔离的可行性。微制造生物胶囊可作为传统聚合物基生物胶囊的替代品，有可能用作体内胰岛素分泌生物反应器。
