Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction
Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction
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DOI：
10.1073/pnas.0602877103
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发表时间：
2006-05-23
影响因子：
11.1
通讯作者：
Lee, Richard T.
中科院分区：
文献类型：
--
作者：
Davis, Michael E.;Hsieh, Patrick C. H.;Lee, Richard T.
心脏修复的策略包括注射细胞，但这些方法受到细胞移植、存活和分化不良的阻碍。为了解决这些缺点，以改善损伤后的心脏功能，我们设计了自组装肽纳米纤维，用于使用“生物素三明治”方法将胰岛素样生长因子1（IGF-1）（一种心肌细胞生长和分化因子）延长递送至心肌。将生物素化的IGF-1与四价链霉亲和素复合，然后与生物素化的自组装肽结合。这种生物素夹心策略允许IGF-1的结合，但不能阻止肽在心肌内自组装成纳米纤维。结合到肽纳米纤维上的IGF-1激活Akt，降低caspase-3的活化，并增加心肌肌钙蛋白1在心肌细胞中的表达。在注射到大鼠心肌中后，生物素化纳米纤维提供了持续28天的IGF-1递送，并且体内IGF-1的靶向递送增加了心肌中Akt的活化。当与移植的心肌细胞结合时，与单独嵌入纳米纤维或未拴系的IGF-1的细胞相比，通过生物素化纳米纤维递送IGF-1使半胱天冬酶-3裂解减少28%，并使肌细胞横截面积增加25%。最后，通过生物素化纳米纤维递送IGF-1的细胞疗法改善了实验性心肌梗死后的收缩功能，证明了工程化局部细胞微环境如何改善细胞疗法。
Strategies for cardiac repair include injection of cells, but theseapproaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiation factor, to the myocardium, using a "biotin sandwich" approach. Biotinylated IGF-1 was complexed with tetravalent streptavidin and then bound to biotinylated self-assembling peptides. This biotin sandwich strategy allowed binding of IGF-1 but did not prevent self-assembly of the peptides into nanofibers within the myocardium. IGF-1 that was bound to pepticle nanofibers activated Akt, decreased activation of caspase-3, and increased expression of cardiac troponin 1 in cardiomyocytes. After injection into rat myocardium, biotinylated nanofibers provided sustained IGF-1 delivery for 28 days, and targeted delivery of IGF-1 in vivo increased activation of Akt in the myocardium. When combined with transplanted cardiomyocytes, IGF-1 delivery by biotinylated nanofibers decreased caspase-3 cleavage by 28% and increased the myocyte cross-sectional area by 25% compared with cells embedded within nanofibers alone or with untethered IGF-1. Finally, cell therapy with IGF-1 delivery by biotinylated nanofibers improved systolic function after experimental myocardial infarction, demonstrating how engineering the local cellular microenvironment can improve cell therapy.