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胰岛玻璃化冷冻保存实现较高的存活率、功能、恢复力和临床移植可扩展性
2022-03-20 15:49
来源：小柯机器人

美国明尼苏达大学Erik B. Finger团队发现胰岛玻璃化冷冻保存实现较高的存活率、功能、恢复力和临床移植可扩展性。相关论文与2022年3月14日在线发表在《自然—医学》杂志上。

据研究人员介绍，胰岛移植可以治愈糖尿病，但需要有足够数量的高质量胰岛。低温保存可以解决胰岛供应链的挑战，因为它可以实现质量控制的银行和捐赠者胰岛的汇集。不幸的是，低温保存并没有成功地实现这一目标，因为它必须同时提供高恢复性、活力、功能和可扩展性。
 
通过全面优化冷冻保护剂（CPA）成分、CPA装载和卸载条件以及玻璃化和复温（VR）的方法，研究人员在小鼠、猪、人和人类干细胞（SC）衍生的β细胞（SC-β）小鼠中实现这一目标。相对于对照组，玻璃化后的胰岛存活率，小鼠为90.5%，SC-β为92.1%，猪为87.2%，人为87.4%，并且在至少9个月的低温保存中保持不变。VR胰岛具有正常的宏观、微观和超微结构的形态。线粒体膜电位和三磷酸腺苷（ATP）水平略有下降，但所有其他的细胞呼吸措施，包括产生ATP的耗氧率（OCR），都没有变化。VR胰岛在体外和体内具有正常的葡萄糖刺激的胰岛素分泌（GSIS）功能。猪和SC-β胰岛在异种移植模型中制造胰岛素，而小鼠胰岛在同种移植模型中得以测试，在移植后24-48小时内，92%的接受者治愈了糖尿病。在150天内，血糖控制效果极佳。
 
最后，这个方法处理了2500个胰岛，胰岛恢复率>95%，解冻后存活率>89%，并且可以随时扩大规模以提高产量。这些结果表明，现在可以用低温保存来提供所需的胰岛来改善移植结果，从而治愈糖尿病。
 
附：英文原文
 
Title: Pancreatic islet cryopreservation by vitrification achieves high viability, function, recovery and clinical scalability for transplantation

Author: Zhan, Li, Rao, Joseph Sushil, Sethia, Nikhil, Slama, Michael Q., Han, Zonghu, Tobolt, Diane, Etheridge, Michael, Peterson, Quinn P., Dutcher, Cari S., Bischof, John C., Finger, Erik B.

Issue&Volume: 2022-03-14

Abstract: Pancreatic islet transplantation can cure diabetes but requires accessible, high-quality islets in sufficient quantities. Cryopreservation could solve islet supply chain challenges by enabling quality-controlled banking and pooling of donor islets. Unfortunately, cryopreservation has not succeeded in this objective, as it must simultaneously provide high recovery, viability, function and scalability. Here, we achieve this goal in mouse, porcine, human and human stem cell (SC)-derived beta cell (SC-beta) islets by comprehensive optimization of cryoprotectant agent (CPA) composition, CPA loading and unloading conditions and methods for vitrification and rewarming (VR). Post-VR islet viability, relative to control, was 90.5% for mouse, 92.1% for SC-beta, 87.2% for porcine and 87.4% for human islets, and it remained unchanged for at least 9 months of cryogenic storage. VR islets had normal macroscopic, microscopic, and ultrastructural morphology. Mitochondrial membrane potential and adenosine triphosphate (ATP) levels were slightly reduced, but all other measures of cellular respiration, including oxygen consumption rate (OCR) to produce ATP, were unchanged. VR islets had normal glucose-stimulated insulin secretion (GSIS) function in vitro and in vivo. Porcine and SC-beta islets made insulin in xenotransplant models, and mouse islets tested in a marginal mass syngeneic transplant model cured diabetes in 92% of recipients within 24–48h after transplant. Excellent glycemic control was seen for 150 days. Finally, our approach processed 2,500 islets with >95% islets recovery at >89% post-thaw viability and can readily be scaled up for higher throughput. These results suggest that cryopreservation can now be used to supply needed islets for improved transplantation outcomes that cure diabetes.

DOI: 10.1038/s41591-022-01718-1

Source: https://www.nature.com/articles/s41591-022-01718-1

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章：《自然—医学》：Online/在线发表

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