Cryopreservation of Whole Rat Livers by Vitrification and Nanowarming

Cryopreservation of Whole Rat Livers by Vitrification and Nanowarming
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通过玻璃化和纳米加温冷冻保存整个大鼠肝脏

DOI:
10.1007/s10439-022-03064-2
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发表时间:
2023
影响因子:
3.8
通讯作者:
Clemens, Mark G.
Clemens, Mark G.
中科院分区:
工程技术2区
文献类型:
--
作者:
Sharma, Anirudh;Lee, Charles Y.;Namsrai, Bat-Erdene;Han, Zonghu;Tobolt, Diane;Rao, Joseph Sushil;Gao, Zhe;Etheridge, Michael L.;Garwood, Michael;Clemens, Mark G.

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肝脏冷冻保存具有实现无限期器官储存的潜力。这项研究研究了玻璃化——在玻璃状状态下对肝脏进行无冰低温保存——作为传统低温保存的一种有希望的替代方法,传统低温保存由于冰的形成或破裂而均匀失败。我们独特的“纳米升温”技术,包括向生物标本灌注冷冻保护剂(CPAs)和二氧化硅涂层氧化铁纳米颗粒(sIONPs),然后,在玻璃化后,通过射频波激发纳米颗粒,使玻璃化标本的再升温足够快,以避免冰的形成,并且足够均匀,以防止热应力开裂,从而解决传统冷冻保存的两个主要缺点。本研究证明了通过血管灌注给大鼠肝脏同时注入CPA和sIONPs的能力,将它们迅速冷却到无冰玻璃化状态,并迅速均匀地重新加热它们。虽然肝酶(丙氨酸转氨酶)有所升高,吲哚菁绿(ICG)排泄受损,但纳米加热后的肝脏仍然存活,保持了正常的组织结构,保留了血管内皮,并显示出肝细胞和器官水平的功能,包括在恒温再灌注过程中产生胆汁和肝细胞摄取ICG。这些发现表明,整个肝脏的低温保存、玻璃化和纳米升温具有实现器官库移植和其他生物医学应用的潜力。
Liver cryopreservation has the potential to enable indefinite organ banking. This study investigated vitrification—the ice-free cryopreservation of livers in a glass-like state—as a promising alternative to conventional cryopreservation, which uniformly fails due to damage from ice formation or cracking. Our unique “nanowarming” technology, which involves perfusing biospecimens with cryoprotective agents (CPAs) and silica-coated iron oxide nanoparticles (sIONPs) and then, after vitrification, exciting the nanoparticlesviaradiofrequency waves, enables rewarming of vitrified specimens fast enough to avoid ice formation and uniformly enough to prevent cracking from thermal stresses, thereby addressing the two main failures of conventional cryopreservation. This study demonstrates the ability to load rat livers with both CPA and sIONPs by vascular perfusion, cool them rapidly to an ice-free vitrified state, and rapidly and homogenously rewarm them. While there was some elevation of liver enzymes (Alanine Aminotransferase) and impaired indocyanine green (ICG) excretion, the nanowarmed livers were viable, maintained normal tissue architecture, had preserved vascular endothelium, and demonstrated hepatocyte and organ-level function, including production of bile and hepatocyte uptake of ICG during normothermic reperfusion. These findings suggest that cryopreservation of whole liversviavitrification and nanowarming has the potential to achieve organ banking for transplant and other biomedical applications.
回应“通过常温机器灌注使每个肝脏都计数增加供体肝脏的移植产量”的评论。
DOI: --
发表时间: 2020
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影响因子: 9
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DOI: --
发表时间: 2008
影响因子: 3.3
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发表时间: 2017-11-01
影响因子: 8.8
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