Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction
Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction
复制标题
间充质干细胞通过神经生长因子增强心肌梗死大鼠模型中的心肌神经萌芽
DOI：
10.2174/13816128113199990451
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发表时间：
2014-04-01
影响因子：
3.1
通讯作者：
Wang, Tong
中科院分区：
文献类型：
--
作者：
Chen, Jian;Zheng, Shaoxin;Wang, Tong
背景资料：骨髓间充质干细胞移植改变大鼠心肌梗死后心室电生理特性。然而，目前还不清楚是否骨髓间充质干细胞移植增强神经生长因子（NGF）的分泌，并影响心脏交感神经remodel.Methods：MI诱导35只雄性SD大鼠。两周后，将动物随机分配到MSC或磷酸盐缓冲溶液（PBS）注射到梗死心肌中。6周后，检测边缘区神经生长因子（NGF）、生长相关蛋白43（GAP 43）和酪氨酸羟化酶（TH）的表达，并计算GAP 43和TH阳性神经密度。结果：与PBS相比，注射MSCs后，边缘区NGF、GAP 43和TH的mRNA表达和蛋白水平均明显升高。免疫组化显示MSCs中GAP 43和TH阳性神经多于PBS组。结论：MSCs移植后神经生长因子表达增加，可能影响心肌梗死后交感神经重构及电生理特性。MSC-CM分泌的旁分泌因子可能参与了这一过程。
Background: Transplantation of mesenchymal stem cells (MSCs) alters the ventricular electrophysiologic properties after myocardial infarction (MI) in rats. However, it is unclear whether MSCs transplantation enhances the secretion of nerve growth factor (NGF) and affects cardiac sympathetic remodeling.Methods: MI was induced in 35 male Sprague-Dawley rats. Two weeks later, the animals were randomized to MSCs or phosphate buffer solution (PBS) injections into the infarcted myocardium. Six weeks thereafter, the expressions of NGF, growth associated protein 43 (GAP43) and tyrosine hydroxylase (TH) were measured and the density of GAP43 and TH positive nerves was calculated in the borderzone. NGF levels were detected in different culture conditions with neonatal rat ventricular myocytes (NRVMs, 2x10(5)/well) and MSCs (2x10(5)/well).Results: Compared with PBS, mRNA expression and protein levels of NGF, GAP43 and TH increased in the border zone after MSCs injection. Immunohistochemistry showed more GAP43- and TH-positive nerves in the MSCs than in the PBS group. Compared to monocultured MSCs, mono-cultured NRVMs secreted more NGF in vitro.Conclusions: The expression of NGF increased after MSCs transplantation, which may affect sympathetic remodeling and the electrophysiological properties after MI. Paracrine factors secreted by MSC-CM may be involved in this process.