Effect of cross-linked hemoglobin on functionality and viability of microencapsulated pancreatic islets
Effect of cross-linked hemoglobin on functionality and viability of microencapsulated pancreatic islets
复制标题
DOI：
10.1089/107632702760184655
复制
发表时间：
2002-06-01
影响因子：
--
通讯作者：
Bae, YH
中科院分区：
文献类型：
--
作者：
Chae, SY;Kim, SW;Bae, YH
在开发用于长期植入胰岛素依赖性糖尿病患者的生物人工胰腺（其由封装的和物理免疫保护的胰岛组成）的许多障碍中，封装的胰岛随时间的功能受损和活力降低是决定植入物的大小和寿命的关键因素。这些因素与从植入部位到笼状胰岛的短氧供应密切相关。为了促进氧转运到胶囊中的胰岛，我们共包封了与双官能聚乙二醇交联的血红蛋白（Hb-缀合物，Hb-C），其尺寸大（>100 kDa），从而防止通过免疫保护膜的扩散损失。通过将Hb-C以0.25 mM的浓度溶解在胰岛悬浮的藻酸盐溶液中，将Hb-C与胰岛共包封在藻酸盐-聚-L-赖氨酸微胶囊中，改善了胰岛的胰岛素分泌和活力。在第0周，在Po-2 = 40 mmHg（假设在最常见的植入部位，腹膜腔中的氧分压）下培养的与Hb-C共包封的胰岛，在100和300 mg/dL的葡萄糖浓度下，与不含Hb-C的对照胰岛相比，多分泌200%的胰岛素。在较高的葡萄糖浓度下，Hb-C效应随着时间的推移变得更加显著。在40 mmHg下培养胰岛8周后，与对照相比，在葡萄糖浓度为100和300 mg/dL时，胰岛素分泌分别增加200和550%。结果与改善的存活率密切相关，并表明Hb-C的引入是维持对包封胰岛的氧供应的有效方法。此外，Hb-C与胰岛的共包封可以（1）提供减小生物杂交人工胰腺的大尺寸的部分线索，（2）导致对胰腺捐赠的需求减少，以及（3）延长生物杂交人工胰腺在体内的寿命。
Of many obstacles involved in developing a bioartificial pancreas, which consists of encapsulated and physically immunoprotected islets, for long-term implantation in insulin-dependent diabetic patients, the impaired functionality and decreasing viability of encapsulated islets over time are critical factors in determining the size and longevity of the implant. These factors are closely associated with short oxygen supply to the encaged islets from the implant site. To facilitate oxygen transport to islets in the capsules, we coencapsulated hemoglobin cross-linked with difunctional polyethylene glycol (Hb-conjugate, Hb-C) which is large in size (>100 kDa), thus preventing diffusional loss through the immunoprotecting membrane. The coencapsulation of Hb-C with islets in alginate-poly-L-lysine microcapsules by dissolving Hb-C in an islet-suspended alginate solution at a concentration of 0.25 mM improved the insulin secretion and viability of the islets. At week 0, the islets, coencapsulated with Hb-C, cultured at Po-2 = 40 mmHg (assumed oxygen partial pressure in the most common implant site, the peritoneal cavity), secreted 200% more insulin compared with the control islets without Hb-C at glucose concentrations of both 100 and 300 mg/dL. The Hb-C effect became more significant with time at higher glucose concentrations. After culturing the islets for 8 weeks at 40 mmHg, the insulin secretion was enhanced 200 and 550% at glucose concentrations of 100 and 300 mg/dL as compared with the control, respectively. The results were closely associated with improved viability and suggest that the introduction of Hb-C is an effective approach to maintaining the oxygen supply to encapsulated islets. In addition, Hb-C coencapsulation with pancreatic islets may (1) provide a partial clue to reducing the large size of the biohybrid artificial pancreas, (2) lead to a reduced need for pancreas donation, and (3) prolong the longevity of the biohybrid artificial pancreas in the body.