Abstract
Mesenchymal stem cells (MSCs) have been proposed as a promising cell population for cell therapy and regenerative medicine applications. However, the low retention and poor survival of engrafted cells hampered the therapeutic efficacy of engrafted MSCs. Ghrelin is a 28-amino-acid peptide hormone and is proved to exert a protective effect on the cardiovascular system. This study is designed to investigate the protective effects of ghrelin on engrafted adipose-derived mesenchymal stem cells (ADMSCs) and its beneficial effects with cellular therapy in mice myocardial infarction (MI). Results showed that intramyocardial injection of ADMSCs combining with ghrelin administration inhibited host cardiomyocyte apoptosis, reduced fibrosis, and improved cardiac function. To reveal possible mechanisms, ADMSCs were subjected to hypoxia/serum deprivation (H/SD) injury to simulate ischemic conditions in vivo. Ghrelin (10−8 M, 33712 pg/ml) improved ADMSCs survival under H/SD condition. Western blot assay revealed that ghrelin increased AKT phosphorylation both in vivo and in vitro, decreased the proapoptotic protein Bax, and increased the antiapoptotic protein Bcl-2 in vitro, while these effects were abolished by PI3K inhibitor LY294002. These revealed that ghrelin may serve as a promising candidate for hormone-driven approaches to improve the efficacy of mesenchymal stem cell-based therapy for cardiac ischemic disease via PI3K/AKT pathway.
Highlights
Ischemic heart disease (IHD) is the leading cause of cardiovascular morbidity and mortality worldwide
Noninvasive bioluminescence imaging (BLI) longitudinally revealed the stable expression of firefly luciferase (Fluc) of adipose-derived mesenchymal stem cells (ADMSCs)
Our results showed that ADMSCs implantation increased PI3K/AKT phosphorylation in mouse heart as compared with myocardial infarction (MI) group, and ADMSCs implantation combined ghrelin administration further increased this trend compared with ADMSCs only (P < 0.05)
Summary
Ischemic heart disease (IHD) is the leading cause of cardiovascular morbidity and mortality worldwide. As was revealed by recent studies, one major challenge for stem cell therapy is the limited survival of engrafted stem cells and its residence in ischemic tissues [2, 3]. This limitation is usually associated with the cells’ unconvincing therapeutic efficacy [4]. Ghrelin is a 28-amino-acid peptide hormone which exerts independent cardiovascular protective actions, such as promoting angiogenesis, reducing myocardial ischemic reperfusion injury, enhancing vasodilation, and alleviating heart failure [5,6,7]. Our previous study revealed that ghrelin promoted the proliferation, migration, and nitric oxide (NO) secretion of cardiac microvascular endothelial cells (CMECs) [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
