title: Ghrelin improves functional survival of engrafted adipose-derived mesenchymal stem cells in ischemic heart through PI3K/Akt signaling pathway.
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, 33,712 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.
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Dong
authors: D
authors: Han
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Wei
authors: W
authors: Huang
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Sai
authors: S
authors: Ma
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Jiangwei
authors: J
authors: Chen
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Lina
authors: L
authors: Gao
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Tong
authors: T
authors: Liu
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Rongqing
authors: R
authors: Zhang
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Xiujuan
authors: X
authors: Li
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Congye
authors: C
authors: Li
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors: Miaomiao
authors: M
authors: Fan
authors: Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors: Yundai
authors: Y
authors: Chen
authors: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China ; Department of Cardiology, Chinese PLA General Hospital, Beijing 100853, China.
authors: Feng
authors: F
authors: Cao
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D064987:Cell- and Tissue-Based Therapy; D054439:Ghrelin / Q000008:administration & dosage*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D054439:Ghrelin; D051028:bcl-2-Associated X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt