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可注射水凝胶通过包含干细胞归巢因子 SDF-1 和血管生成肽 Ac-SDKP 来再生慢性心肌梗死。

Regeneration of chronic myocardial infarction by injectable hydrogels containing stem cell homing factor SDF-1 and angiogenic peptide Ac-SDKP.

机构信息

Korea Artificial Organ Center, Korea University, Seoul 136-705, Republic of Korea.

Korea Artificial Organ Center, Korea University, Seoul 136-705, Republic of Korea; Department of Biomedical Engineering, College of Medicine, Korea University, Seoul 136-705, Republic Korea.

出版信息

Biomaterials. 2014 Mar;35(8):2436-45. doi: 10.1016/j.biomaterials.2013.12.011. Epub 2013 Dec 28.

DOI:10.1016/j.biomaterials.2013.12.011
PMID:24378015
Abstract

Regeneration of chronic myocardial infarction (CMI) is one of the challenging issues due to its limited regeneration activity compared to acute or sub-acute stage. In this study, we examined whether combination of stem cell homing factor (SDF-1) and angiogenic peptides (Ac-SDKP) injected with biomimetic hydrogels promote regeneration of cardiac function in a CMI model. We evaluated the regeneration of chronically infarcted myocardium using injectable biomimetic hydrogels containing two therapeutic factors; stromal-derived factor-1 (SDF-1) and Ac-SDKP for stem cell homing and angiogenesis, respectively. Injection of the two therapeutic factors into the infarct region of the left ventricle showed that the biomimetic hydrogels containing two therapeutic factor exhibited significantly improved left ventricle function, increased angiogenesis, decreased infarct size and greatest wall thickness within the infarct region at 4 weeks post-treatment. From these results, it is clear that hydrogels containing two therapeutic factors showed synergistic effects on regeneration in the chronic heart failure model. In conclusion, these results suggest that combination of stem cell homing factor with angiogenic peptides recruit stem cells to the microenvironments, increase the expression of angiogenic genes, enhance the matured vessel formation and improve the cardiac function in chronic MI.

摘要

慢性心肌梗死(CMI)的再生是一个具有挑战性的问题,因为与急性或亚急性期相比,其再生活性有限。在这项研究中,我们研究了将干细胞归巢因子(SDF-1)和血管生成肽(Ac-SDKP)与仿生水凝胶联合使用是否能促进 CMI 模型中心脏功能的再生。我们使用含有两种治疗因子的可注射仿生水凝胶评估慢性梗死心肌的再生;基质衍生因子-1(SDF-1)和 Ac-SDKP 分别用于干细胞归巢和血管生成。将两种治疗因子注射到左心室梗死区域后,结果表明,含有两种治疗因子的仿生水凝胶可显著改善左心室功能,增加血管生成,减少梗死面积,并在治疗后 4 周内使梗死区域的壁厚度最大。从这些结果可以清楚地看出,含有两种治疗因子的水凝胶在慢性心力衰竭模型中的再生中表现出协同作用。总之,这些结果表明,干细胞归巢因子与血管生成肽的联合使用可将干细胞募集到微环境中,增加血管生成基因的表达,增强成熟血管的形成,并改善慢性 MI 的心脏功能。

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