A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based heparin hydrogels and improves eEPC migration in vitro
A novel, biased-like SDF-1 derivative acts synergistically with starPEG-based heparin hydrogels and improves eEPC migration in vitro
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DOI：
10.1016/j.jconrel.2012.04.049
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发表时间：
2012-08-20
影响因子：
10.8
通讯作者：
Beck-Sickinger, Annette G.
中科院分区：
文献类型：
--
作者：
Baumann, Lars;Prokoph, Silvana;Beck-Sickinger, Annette G.
CXC 趋化因子基质细胞衍生因子 1 α（SDF-1 α、CXCL12）已被证明可以将不同来源的 CXCR4 阳性干细胞和祖细胞募集到缺损的心脏部位，具有显着的临床益处。然而，炎症相关蛋白酶的快速蛋白水解失活、不准确的药物输送或不适当的局部浓度属于可行应用的最大缺点。在此，我们提出了一种可转换的、偏向的 SDF-1 α 变体，AAV-[S4V]-SDF-1 α，其独特的活性与炎症相关的二肽基肽酶 4 (DPP-4) 的存在相结合，该酶可从前体中裂解丙氨酸-丙氨酸二肽。我们用我们的新型 SDF-1 α 变体装饰 starPEG-肝素水凝胶，并在体外测试它们的固定效率、时间依赖性蛋白质释放以及早期内皮祖细胞 (eEPC) 的动员。我们发现与传统的 SDF-1 α 相比，迁移率更高。总之，我们提供了关于酶促激活 SDF-1 α 和 starPEG-肝素水凝胶协同效应的概念性工作。 (C) 2012 Elsevier B.V. 保留所有权利。
The CXC chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha, CXCL12) has been proven to recruit CXCR4 positive stem and progenitor cells of different sources to defected heart sites, with significant clinical benefits. However, the rapid proteolytic inactivation by inflammation-related proteases, inaccurate drug delivery or inappropriate local concentrations belong to the largest disadvantages for feasible application. Herein, we present a switchable, biased-like SDF-1 alpha variant, AAV-[S4V]-SDF-1 alpha, whose distinct activity is coupled to the inflammation-associated presence of dipeptidylpeptidase-4 (DPP-4), which cleaves an alanine-alanine dipeptide from the precursor. We decorated starPEG-heparin hydrogels with our novel SDF-1 alpha variant and tested them for immobilization efficiency, time-dependent protein release as well as mobilization of early endothelial progenitor cells (eEPCs) in vitro. We found higher migration rates compared to conventional SDF-1 alpha. In summary, we provide a conceptual work on cooperative effects of enzymatically activatable SDF-1 alpha and starPEG-heparin hydrogels. (C) 2012 Elsevier B. V. All rights reserved.