Hayashi H, Inoue K, Aung T, Tun T, Yuanjun G, Wenjing W, Shinohara S, Kaji H, Doi R, Setoyama H, Kato M, Imamura M, Maetani S, Morikawa N, Iwata H, Ikada Y, Miyazaki J
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Cell Transplant. 1996 Sep-Oct;5(5 Suppl 1):S65-9. doi: 10.1016/0963-6897(96)00043-7.
This study examines the function of a novel B cell line (MIN6) enclosed in hybrid bioartificial pancreas with mesh-reinforced polyvinyl alcohol hydrogel tube (MRPT) or with improved, three-layer agarose microcapsules. MIN6 was established from insulinomas obtained by targeted expression of the simian virus 40 T-antigen gene in transgenic mice. MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. The MRPT and the three-layer agarose microcapsules, which were developed to act as an artificial pancreas, were readily permeated by insulin, glucose, and other nutrients. Both can immunoisolate enclosed MIN6 cells from the recipient's humoral and cellular immunosystems, which causes a xenogeneic rejection response. MIN6 cells (5.0 x 10(6) or 1.5 x 10(6)) were enclosed in MRPT or in a hundred three-layer microcapsules and subjected to an in vitro perifusion study or a static incubation study to observe the insulin release from each bioartificial pancreas in response to glucose stimulation. In vitro study revealed that the insulin secretion in response to 16.7 mM glucose stimulation was twice that with 3.3 mM glucose stimulation with both MRPT and the three-layer agarose microcapsules. The present study demonstrates that MIN6 effectively functions as a bioreactor for the hybrid bioartificial pancreas. The application of MIN6 cells to the hybrid bioartificial pancreas may offer a solution to the current serious dearth of organs.
本研究考察了一种新型B细胞系（MIN6）在带有网状增强聚乙烯醇水凝胶管（MRPT）或改良的三层琼脂糖微胶囊的混合生物人工胰腺中的功能。MIN6是通过在转基因小鼠中靶向表达猿猴病毒40 T抗原基因从胰岛素瘤中建立的。MIN6保留了在生理葡萄糖浓度下分泌胰岛素的能力。被开发用作人工胰腺的MRPT和三层琼脂糖微胶囊很容易被胰岛素、葡萄糖和其他营养物质渗透。两者都能将包封的MIN6细胞与受体的体液和细胞免疫系统免疫隔离，而后者会引发异种排斥反应。将MIN6细胞（5.0×10⁶或1.5×10⁶）包封在MRPT或一百个三层微胶囊中，并进行体外灌注研究或静态孵育研究，以观察每种生物人工胰腺在葡萄糖刺激下的胰岛素释放情况。体外研究表明，在16.7 mM葡萄糖刺激下的胰岛素分泌量是在3.3 mM葡萄糖刺激下的两倍，MRPT和三层琼脂糖微胶囊均如此。本研究表明，MIN6有效地充当了混合生物人工胰腺的生物反应器。将MIN6细胞应用于混合生物人工胰腺可能为当前严重的器官短缺问题提供一种解决方案。
