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人脐带华通氏胶间充质干细胞移植对心肌损伤大鼠模型的心脏保护作用

Cardioprotective Effects of Wharton Jelly Derived Mesenchymal Stem Cell Transplantation in a Rodent Model of Myocardial Injury.

作者信息

Gaafar Taghrid, Attia Wael, Mahmoud Shereen, Sabry Dina, Aziz Osama Abdel, Rasheed Dina, Hamza Hala

机构信息

Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Department of Pediatric Cardiology, Faculty of Medicine, Cairo University, Cairo, Egypt.

出版信息

Int J Stem Cells. 2017 May 30;10(1):48-59. doi: 10.15283/ijsc16063.

Abstract

BACKGROUND

Whartons jelly-derived mesenchymal stem cells are a valuable alternative source that possess multipotent properties, easy to obtain and available in large scale compared to BMMSCs. We investigated the possibility of cardiac function improvement post isoproterenol induced cardiac injury in a rat model following human WJMSCs transplantation.

MATERIALS AND METHODS

MSCs were extracted and cultured from cord WJ, characterized by morphology, Immunophenotyping and differentiation to osteoblast and adipocytes. WJMSCs were labeled with PKH2 linker dye. Wistar rats were divided into control group, ISO group (injected with 2 doses of isoproterenol) to induce myocardial injury and ISO group transplanted with labelled WJMSCs. ECG, electrocardiographic patterns, cardiac marker enzymes, tracing of labeled MSCs and immunohistochemical analysis of myocardial cryosections were studied.

RESULTS AND CONCLUSIONS

WJ derived MSCs were expanded for more than 14 passages while maintaining their undifferentiated state, were positive for MSC markers and were able to differentiate into adipocyte and osteoblast. We demonstrated that intravenously administered WJMSCs were capable of homing predominently in the ischemic myocardium. Cardiac markers were positively altered in stem cell treated group compared to ISO group. ECG and ECHO changes were improved with higher survival rate. WJMSCs could differentiate into cardiac-like cells (positive for cardiac specific proteins) in vivo. WJMSCs infusion promoted cardiac protection and reduced mortality, emphasizing a promising therapeutic role for myocardial insufficiency.

摘要

背景

与骨髓间充质干细胞相比,脐带来源的间充质干细胞是一种有价值的替代来源,具有多能特性,易于获取且可大规模获得。我们研究了在异丙肾上腺素诱导的大鼠心脏损伤模型中,人脐带来源的间充质干细胞移植后改善心脏功能的可能性。

材料与方法

从脐带华通氏胶中提取并培养间充质干细胞,通过形态学、免疫表型分析以及向成骨细胞和脂肪细胞的分化进行鉴定。用PKH2连接染料标记脐带来源的间充质干细胞。将Wistar大鼠分为对照组、ISO组(注射两剂异丙肾上腺素以诱导心肌损伤)和移植了标记的脐带来源的间充质干细胞的ISO组。研究了心电图、心脏标志物酶、标记的间充质干细胞的追踪以及心肌冰冻切片的免疫组织化学分析。

结果与结论

从脐带中分离出的间充质干细胞在保持未分化状态的情况下传代培养超过14代,对间充质干细胞标志物呈阳性反应,并能够分化为脂肪细胞和成骨细胞。我们证明静脉注射的脐带来源的间充质干细胞能够主要归巢到缺血心肌中。与ISO组相比,干细胞治疗组的心脏标志物呈正向改变。心电图和超声心动图变化得到改善,存活率更高。脐带来源的间充质干细胞在体内可分化为类心肌细胞(对心脏特异性蛋白呈阳性)。脐带来源的间充质干细胞输注促进了心脏保护并降低了死亡率,强调了其在心肌功能不全治疗中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c4d/5488776/d0028ee67016/ijsc-10-048f1.jpg

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