Institute of Biochemistry, Faculty of Biosciences, Pharmacy and Psychology, Universität Leipzig, Germany.
J Control Release. 2012 Aug 20;162(1):68-75. doi: 10.1016/j.jconrel.2012.04.049. Epub 2012 May 22.
The CXC chemokine stromal cell-derived factor-1α (SDF-1α, 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-1α variant, AAV-[S4V]-SDF-1α, 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-1α 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-1α. In summary, we provide a conceptual work on cooperative effects of enzymatically activatable SDF-1α and starPEG-heparin hydrogels.
趋化因子 CXC 基质细胞衍生因子-1α（SDF-1α，CXCL12）已被证明可招募不同来源的 CXCR4 阳性干细胞和祖细胞到缺陷心脏部位，具有显著的临床益处。然而，炎症相关蛋白酶的快速蛋白水解失活、药物传递不准确或局部浓度不当是其可行应用的最大缺点。在这里，我们提出了一种可切换的、类似偏向的 SDF-1α 变体，AAV-[S4V]-SDF-1α，其独特的活性与炎症相关的二肽基肽酶-4（DPP-4）的存在相关联，DPP-4 从前体中切割出一个丙氨酰-丙氨酸二肽。我们用我们的新型 SDF-1α 变体对星 PEG-肝素水凝胶进行了修饰，并测试了它们的固定化效率、随时间释放的蛋白以及体外早期内皮祖细胞（eEPC）的动员情况。与传统的 SDF-1α 相比，我们发现迁移率更高。总之，我们提供了一个关于酶激活的 SDF-1α 和星 PEG-肝素水凝胶的协同作用的概念性工作。
