低温保存海藻酸盐包封胰岛比低温保存未包封胰岛能更好地恢复糖尿病动物模型的正常血糖。

Cell medicine Pub Date : 2019-09-13 eCollection Date: 2019-01-01 DOI:10.1177/2155179019876641
Greg G Kojayan, Antonio Flores, Shiri Li, Michael Alexander, Jonathan Rt Lakey
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引用次数: 8

摘要

胰岛移植在临床上已被证明可以恢复正常血糖。目前临床上广泛应用胰岛移植的限制之一是培养和保存超过100万个胰岛当量,为移植做准备。一个可能的解决方案是将冷冻的胰岛储存起来,以便在需要时使用。虽然有希望,但标准的胰岛冷冻方案引入了压力和细胞死亡,导致解冻后胰岛质量的高度可变性。本研究旨在开发一种改进的低温保存方案,使用海藻酸盐包封的胰岛来提高胰岛的存活率和功能,为未来的移植做准备。我们的数据显示,包封可以改善冷冻胰岛解冻后的胰岛存活率和功能。冷冻封装的胰岛在解冻后的胰岛产量回收率为84%,而非封装的胰岛产量回收率为72%。解冻后未包裹的胰岛存活率为78%,而包裹的胰岛存活率为88%。解冻后进行静态葡萄糖测试,未包封组、1.75%海藻酸盐组和2.5%海藻酸盐组的刺激指数分别为1.9±0.5、2.9±0.1和3.3±0.3。在一项移植研究中,接受1.75%海藻酸包裹的冷冻保存胰岛的小鼠在移植后平均5天达到正常血糖。相比之下,接受新鲜胰岛的对照组小鼠需要4天,而接受未封装的冷冻保存胰岛的对照组需要18天。总之,冷冻前用1.75%海藻酸盐包封胰岛,与不包封的胰岛相比,可以显著提高胰岛的存活率、解冻后的功能和移植物反应。
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Cryopreserved Alginate-Encapsulated Islets Can Restore Euglycemia in a Diabetic Animal Model Better than Cryopreserved Non-encapsulated Islets.

Islet transplantation has been shown to restore normoglycemia clinically. One of the current limitations to the widespread clinical use of islet transplantation is culturing and preserving more than 1 million islet equivalents in preparation for transplant. One possible solution is to bank frozen islets and use them when needed. Although promising, the standard islet freezing protocol introduces stress and cell death, resulting in high variability of islet quality post thawing. This study aimed to develop an improved cryopreservation protocol using alginate-encapsulated islets to improve islet survival and function for future transplants. Our data showed that encapsulation improved islet survival and function after thawing the frozen islets. Frozen encapsulated islets have an islet yield recovery of 84% when compared to non-encapsulated islets at 72% after thawing. Post-thaw viability was 78% for non-encapsulated islets compared to 88% for encapsulated islets. The stimulation index values after a static glucose test following thawing were 1.9 ± 0.5, 2.9 ± 0.1, and 3.3 ± 0.3 for the non-encapsulated, 1.75% alginate, and 2.5% alginate groups, respectively. In a transplant study, the mice that received 1.75% alginate-encapsulated cryopreserved islets achieved normoglycemia on average 5 days after transplant. In comparison, control mice that received fresh islets took 4 days, while those receiving unencapsulated cryopreserved islets took 18 days. In conclusion, encapsulating islets in 1.75% alginate prior to freezing was shown to improve islet survival, function post thawing, and graft response significantly when compared to islets frozen without encapsulation.

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Cell medicine
Cell medicine MEDICINE, RESEARCH & EXPERIMENTAL-
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