Maintenance of ischemic β cell viability through delivery of lipids and ATP by targeted liposomes.
Maintenance of ischemic β cell viability through delivery of lipids and ATP by targeted liposomes.
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DOI：
10.1039/c3bm60094g
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发表时间：
2014-04-01
影响因子：
6.6
通讯作者：
Kokkoli E
中科院分区：
文献类型：
--
作者：
Atchison N;Swindlehurst G;Papas KK;Tsapatsis M;Kokkoli E
胰岛移植是治疗1型糖尿病的一种很有前途的治疗方法，但尽管取得了成功，但现有的挑战阻碍了广泛应用。缺血，发生在胰腺保存和分离，以及胰岛移植后，降低胰岛的活力和功能。我们假设脂质体递送三磷酸腺苷（ATP）可以防止缺血损伤期间细胞活力的丧失。本研究以INS-1为模型细胞，研究了脂质体与缺血β细胞的相互作用，并考察了纤连蛋白模拟肽PR_B修饰的脂质体促进ATP向缺血β细胞转运的能力。我们证明PR_B增加了脂质体与β细胞的结合和内化。出乎意料的是，当比较有和没有ATP的PR_B脂质体保护INS-1细胞免于缺血的能力时，我们发现两种制剂都增加了细胞存活。通过研究含有和不含ATP的PR_B功能化脂质体处理的缺血细胞的功能活性，我们发现脂质和ATP在缺血损伤后维持细胞代谢活性和防止细胞坏死中起作用。这种方法可能有利于防止缺血相关的胰岛细胞损伤，特别是在器官保存阶段。
Islet transplantation is a promising treatment for type 1 diabetes, but despite the successes, existing challenges prevent widespread application. Ischemia, occurring during pancreas preservation and isolation, as well as after islet transplantation, decreases islet viability and function. We hypothesized that the liposomal delivery of adenosine triphosphate (ATP) could prevent the loss of cell viability during an ischemic insult. In this work we use a model β cell line, INS-1 to probe the liposome/cell interactions and examined the ability of liposomes functionalized with the fibronectin-mimetic peptide PR_b to facilitate the delivery of ATP to ischemic β cells. We demonstrate that PR_b increases the binding and internalization of liposomes to the β cells. Unexpectedly, when comparing the ability of PR_b liposomes with and without ATP to protect INS-1 cells from ischemia we found that both formulations increased cell survival. By probing the functional activity of ischemic cells treated with PR_b functionalized liposomes with and without ATP we find that both lipids and ATP play a role in maintaining cell metabolic activity after an ischemic insult and preventing cell necrosis. This approach may be beneficial for preventing ischemia related damage to islet cells, especially in the organ preservation stage.