整合素连接激酶过表达的 Sca-1+ 心脏祖细胞治疗可改善心肌梗死后的心脏功能。

Sca-1+ cardiac progenitor cell therapy with cells overexpressing integrin-linked kinase improves cardiac function after myocardial infarction.

机构信息

Department of Cardiology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.

出版信息

Transplantation. 2013 May 27;95(10):1187-96. doi: 10.1097/TP.0b013e31828a9423.

DOI:10.1097/TP.0b013e31828a9423

PMID:23598943

Abstract

BACKGROUND

This study was to investigate the effect of integrin-linked kinase (ILK) on the transplantation efficiency of stem cell antigen-1-positive cardiac progenitor cells (Sca-1 CPCs) in a mouse myocardial infarction (MI) model.

METHODS

Sca-1 CPCs were isolated from C57/BL6 mice heart tissues and genetically modified with adenovirus vector containing green fluorescent protein (GFP)/ILK or GFP. Cell viability, migration, DNA synthesis, proliferation, and apoptosis were assessed in vitro. Immediately after MI, treated animals received 5×10 GFP-CPC or ILK-CPC transplantation into the peri-infarct myocardium. Cardiac function, exercise ability, cardiac morphology, angiogenesis, cardiomyocyte apoptosis, as well as ILK-related protein expression were measured. Acute and long-term cell survival after cell transplantation was assessed.

RESULTS

Overexpression of ILK increased the viability, migration, DNA synthesis, proliferation, and survival of Sca-1 CPCs in vitro. Protein expression of phosphorylated Akt and cyclin D1 were up-regulated. In our in vivo experiment, more transplanted cells were found in the peri-infarct myocardium in ILK-CPC group 3 days after cell transplantation, but there was no difference between the two groups 4 weeks later. ILK-CPC group showed reduced infarct size 7 days after cell transplantation. Long-term observation showed improved cardiac function indicated by higher percent fractional shortening and lower left ventricular end systolic diameter/left ventricular end diastolic diameter, better exercise ability, increased angiogenesis, decreased fibrosis and apoptosis, as well as up-regulation of ILK, Cdc42, and Aurora B protein expression in ILK-CPC group 4 weeks after cell transplantation.

CONCLUSIONS

ILK-overexpressed Sca-1 CPCs showed improved therapeutic efficacy in MI.

摘要

背景

本研究旨在探讨整合素连接激酶（ILK）对干细胞抗原-1 阳性心肌祖细胞（Sca-1 CPCs）在小鼠心肌梗死（MI）模型中移植效率的影响。

方法

从 C57/BL6 小鼠心脏组织中分离 Sca-1 CPCs，并通过含有绿色荧光蛋白（GFP）/ILK 或 GFP 的腺病毒载体进行基因修饰。在体外评估细胞活力、迁移、DNA 合成、增殖和凋亡。在 MI 后立即，将处理后的动物接受 5×10 GFP-CPC 或 ILK-CPC 移植到梗死周边心肌。测量心功能、运动能力、心脏形态、血管生成、心肌细胞凋亡以及与 ILK 相关的蛋白表达。评估细胞移植后的急性和长期细胞存活。

结果

ILK 的过表达增加了 Sca-1 CPCs 的体外活力、迁移、DNA 合成、增殖和存活。磷酸化 Akt 和细胞周期蛋白 D1 的蛋白表达上调。在我们的体内实验中，细胞移植后 3 天，ILK-CPC 组在梗死周边心肌中发现更多的移植细胞，但 4 周后两组之间没有差异。ILK-CPC 组在细胞移植后 7 天显示出梗死面积减小。长期观察显示，ILK-CPC 组的心脏功能改善，表现为更高的百分比较短、更低的左心室收缩末期直径/左心室舒张末期直径，更好的运动能力，增加的血管生成，减少的纤维化和凋亡，以及 ILK、Cdc42 和 Aurora B 蛋白表达的上调。