Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction

Jian      Chen; Shaoxin      Zheng; Hui      Huang; Suihua      Huang; Changqing      Zhou; Jingying      Hou; Jieyu      Jiang; Jingfeng      Wang; Wei      Wu; Tong      Wang

doi:10.2174/13816128113199990451

Abstract

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, 2×10⁵/well) and MSCs (2×10⁵/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.

Keywords: Mesenchymal stem cells, myocardial infarction, nerve growth factor, sympathetic remodeling, paracrine effects, electrophysiology, growth associated protein 43, tyrosine hydroxylase.