白细胞介素-7 在大鼠骨髓间充质干细胞与心肌细胞体外融合及改善体内心功能中的作用。

Role of interleukin-7 in fusion of rat bone marrow mesenchymal stem cells with cardiomyocytes in vitro and improvement of cardiac function in vivo.

机构信息

Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

Department of Biochemistry, University of Karachi, Karachi, Pakistan.

出版信息

Cardiovasc Ther. 2018 Dec;36(6):e12479. doi: 10.1111/1755-5922.12479. Epub 2018 Dec 6.

DOI:10.1111/1755-5922.12479

PMID:30451388

Abstract

AIMS

Mesenchymal stem cells (MSCs) hold significant promise as potential therapeutic candidates following cardiac injury. However, to ensure survival of transplanted cells in ischemic environment, it is beneficial to precondition them with growth factors that play important role in cell survival and proliferation. Aim of this study is to use interleukin-7 (IL-7), a cell survival growth factor, to enhance the potential of rat bone marrow MSCs in terms of cell fusion in vitro and cardiac function in vivo.

METHODS

Mesenchymal stem cells were transfected with IL-7 gene through retroviral vector. Normal and transfected MSCs were co-cultured with neonatal cardiomyocytes (CMs) and cell fusion was analyzed by flow cytometry and fluorescence microscopy. These MSCs were also transplanted in rat model of myocardial infarction (MI) and changes at tissue level and cardiac function were assessed by histological analysis and echocardiography, respectively.

RESULTS

Co-culture of IL-7 transfected MSCs and CMs showed significantly higher (P < 0.01) number of fused cells as compared to normal MSCs. Histological analysis of hearts transplanted with IL-7 transfected MSCs showed significant reduction (P < 0.001) in infarct size and better preservation (P < 0.001) of left ventricular wall thickness as compared to normal MSCs. Presence of cardiac-specific proteins, α-actinin, and troponin-T showed that the transplanted MSCs were differentiated into cardiomyocytes. Echocardiographic recordings of the experimental group transplanted with transfected MSCs showed significant increase in the ejection fraction and fractional shortening (P < 0.01), and decrease in diastolic and systolic left ventricular internal diameters (P < 0.001) and end systolic and diastolic volumes (P < 0.01 and P < 0.001, respectively).

CONCLUSION

Interleukin-7 is able to enhance the fusogenic properties of MSCs and improve cardiac function. This improvement may be attributed to the supportive action of IL-7 on cell proliferation and cell survival contributing to the regeneration of damaged myocardium.

摘要

目的

间充质干细胞（MSCs）在心脏损伤后作为潜在的治疗候选物具有重要意义。然而，为了确保移植细胞在缺血环境中的存活，用在细胞存活和增殖中起重要作用的生长因子对其进行预处理是有益的。本研究的目的是使用白细胞介素-7（IL-7），一种细胞存活生长因子，来提高大鼠骨髓间充质干细胞在体外细胞融合和体内心脏功能方面的潜力。

方法

通过逆转录病毒载体将 IL-7 基因转染到间充质干细胞中。将正常和转染的间充质干细胞与新生心肌细胞（CMs）共培养，并通过流式细胞术和荧光显微镜分析细胞融合。这些间充质干细胞也被移植到大鼠心肌梗死（MI）模型中，通过组织水平的组织学分析和心脏功能的超声心动图分别评估组织水平和心脏功能的变化。

结果

与正常间充质干细胞相比，IL-7 转染的间充质干细胞与 CMs 的共培养显示出显著更高（P<0.01）的融合细胞数量。移植 IL-7 转染的间充质干细胞的心脏组织学分析显示，与正常间充质干细胞相比，梗死面积显著减少（P<0.001），左室壁厚度的保存更好（P<0.001）。存在心脏特异性蛋白肌动蛋白和肌钙蛋白-T 表明移植的间充质干细胞已分化为心肌细胞。转染间充质干细胞实验组的超声心动图记录显示，射血分数和缩短分数显著增加（P<0.01），舒张和收缩左室内径（P<0.001）以及收缩末期和舒张末期容积（P<0.01 和 P<0.001）均显著减少。