Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction
| Autor: | Yu Huang, Hong Huashan, Yunling Lin, Wenying Wang, Yukun Luo, Yilang Ke, Jun Fang, DanQing Hu, ShuMei Li, TingXiang Lan, HuiYa Li, DeDong Zheng, Guilin Chen, Lingzhen Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cell death
Male Cancer Research Immunology Myocardial Infarction Pharmacology Article Cell therapy Rats Sprague-Dawley Cellular and Molecular Neuroscience Paracrine signalling In vivo Medicine Animals Protein kinase B QH573-671 business.industry Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Blood Proteins Cytoprotection Rats Transplantation Stem cell Cytology business Peptides Heart stem cells |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 12, Iss 6, Pp 1-11 (2021) |
| ISSN: | 2041-4889 |
| Popis: | 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-α and interleukin-1β 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. |
| Databáze: | OpenAIRE |
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