De Vos P, De Haan B J, Wolters G H, Strubbe J H, Van Schilfgaarde R
Department of Surgery, University of Groningen, The Netherlands.
Diabetologia. 1997 Mar;40(3):262-70. doi: 10.1007/s001250050673.
Graft failure of alginate-polylysine microencapsulated islets is often interpreted as the consequence of a non-specific foreign body reaction against the microcapsules, initiated by impurities present in crude alginate. The aim of the present study was to investigate if purification of the alginate improves the biocompatibility of alginate-polylysine microcapsules. Alginate was purified by filtration, extraction and precipitation. Microcapsules prepared from crude or purified alginate were implanted in the peritoneal cavity of normoglycaemic AO-rats and retrieved at 1, 2, 3, 6, 9, and 12 months after implantation. With crude alginate, all capsules were overgrown within 1 month after implantation. With purified alginate, however, the portion of capsules overgrown was usually less than 10%, even at 12 months after implantation. All recipients of islet allografts in capsules prepared of purified alginate became normoglycaemic within 5 days after implantation, but hyperglycaemia reoccurred after 6 to 20 weeks. With intravenous and oral glucose tolerance test, all recipients had impaired glucose tolerance and insulin responses were virtually absent. After graft failure, capsules were retrieved (80-100%) by peritoneal lavage. Histologically, the percentage of overgrown capsules was usually less than 10% and maximally 31%. This small portion cannot explain the occurrence of graft failure. The immunoprotective properties of the capsules were confirmed by similar if not identical survival times of encapsulated islet allo- and isografts. Our results show that purification of the alginate improves the biocompatibility of alginate-polylysine microcapsules. Nevertheless, graft survival was still limited, most probably as a consequence of a lack of blood supply to the encapsulated islets.
藻酸盐-聚赖氨酸微囊化胰岛的移植失败通常被解释为是由粗制藻酸盐中存在的杂质引发的针对微囊的非特异性异物反应所致。本研究的目的是调查藻酸盐的纯化是否能改善藻酸盐-聚赖氨酸微囊的生物相容性。藻酸盐通过过滤、萃取和沉淀进行纯化。用粗制或纯化后的藻酸盐制备的微囊被植入血糖正常的AO大鼠的腹腔，并在植入后1、2、3、6、9和12个月取出。使用粗制藻酸盐时，所有微囊在植入后1个月内均被过度生长的组织覆盖。然而，使用纯化后的藻酸盐时，即使在植入后12个月，微囊被过度生长组织覆盖的比例通常也不到10%。所有接受纯化藻酸盐制备的微囊中胰岛同种异体移植的受体在植入后5天内血糖恢复正常，但在6至20周后再次出现高血糖。通过静脉和口服葡萄糖耐量试验，所有受体的葡萄糖耐量均受损，几乎没有胰岛素反应。移植失败后，通过腹腔灌洗可取出80%-100%的微囊。组织学检查显示，微囊被过度生长组织覆盖的百分比通常不到10%，最大为31%。如此小的比例无法解释移植失败的发生。微囊的免疫保护特性通过包封的胰岛同种异体移植和同基因移植相似（即使不完全相同）的存活时间得到证实。我们的结果表明，藻酸盐的纯化改善了藻酸盐-聚赖氨酸微囊的生物相容性。然而，移植存活时间仍然有限，很可能是由于包封的胰岛缺乏血液供应所致。
