PMID- 34006853 OWN - NLM STAT- MEDLINE DCOM- 20211014 LR - 20211014 IS - 2041-4889 (Electronic) VI - 12 IP - 6 DP - 2021 May 18 TI - Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction. PG - 505 LID - 10.1038/s41419-021-03610-1 [doi] LID - 505 AB - Both weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-alpha and interleukin-1beta in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways. FAU - Li, HuiYa AU - Li H AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. AD - YinZhou People's Hospital & Affiliated Hospital, Medical School, Ningbo University, Ningbo, PR China. FAU - Hu, DanQing AU - Hu D AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Chen, Guilin AU - Chen G AD - Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, PR China. FAU - Zheng, DeDong AU - Zheng D AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. AD - Department of Emergency, People's Hospital of Longhua, Shenzhen, PR China. FAU - Li, ShuMei AU - Li S AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Lin, YunLing AU - Lin Y AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Hong, HuaShan AU - Hong H AD - Department of Geriatrics, Fujian Key Laboratory of Vascular Aging, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Luo, Yukun AU - Luo Y AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Ke, YiLang AU - Ke Y AD - Department of Geriatrics, Fujian Key Laboratory of Vascular Aging, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Huang, Yu AU - Huang Y AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Wu, LingZhen AU - Wu L AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Lan, TingXiang AU - Lan T AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Wang, WenYing AU - Wang W AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. FAU - Fang, Jun AU - Fang J AUID- ORCID: 0000-0003-4243-0861 AD - Department of Cardiology, Fujian Institute of Coronary Heart Disease, Fujian Heart Medical Center, Fujian Medical University Union Hospital, Fuzhou, PR China. ptfangjun@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210518 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Blood Proteins) RN - 0 (ENHO protein, rat) RN - 0 (Peptides) SB - IM MH - Animals MH - Blood Proteins/*pharmacology MH - Male MH - Mesenchymal Stem Cells/*drug effects/metabolism MH - Myocardial Infarction/*drug therapy/metabolism MH - Peptides/*pharmacology MH - Rats MH - Rats, Sprague-Dawley PMC - PMC8131743 COIS- The author declares no competing interests. EDAT- 2021/05/20 06:00 MHDA- 2021/10/15 06:00 PMCR- 2021/05/18 CRDT- 2021/05/19 06:12 PHST- 2020/08/07 00:00 [received] PHST- 2021/03/11 00:00 [accepted] PHST- 2021/03/05 00:00 [revised] PHST- 2021/05/19 06:12 [entrez] PHST- 2021/05/20 06:00 [pubmed] PHST- 2021/10/15 06:00 [medline] PHST- 2021/05/18 00:00 [pmc-release] AID - 10.1038/s41419-021-03610-1 [pii] AID - 3610 [pii] AID - 10.1038/s41419-021-03610-1 [doi] PST - epublish SO - Cell Death Dis. 2021 May 18;12(6):505. doi: 10.1038/s41419-021-03610-1.