Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction.
Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction.
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基于Adropin的双重治疗增强间充质干细胞对大鼠心肌梗死的治疗潜力
DOI：
10.1038/s41419-021-03610-1
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发表时间：
2021-05-18
影响因子：
9
通讯作者：
Fang J
中科院分区：
文献类型：
--
作者：
Li H;Hu D;Chen G;Zheng D;Li S;Lin Y;Hong H;Luo Y;Ke Y;Huang Y;Wu L;Lan T;Wang W;Fang J
干细胞生存能力弱和微环境恶劣是细胞治疗的双重困境。 Adropin 是一种生物活性物质，已被证明具有细胞保护作用。因此，我们假设，通过采用基于adropin的双重治疗，促进体外干细胞存活和改变体内微环境，adropin可能对心肌梗死干细胞的治疗潜力产生双重保护作用。在当前的研究中，adropin (25 ng/ml) 在体外可减少过氧化氢诱导的大鼠骨髓间充质干细胞 (MSC) 细胞凋亡，并通过增加 Akt 和细胞外调节蛋白激酶 (ERK) l/2 的磷酸化来提高 MSC 的存活率。 Adropin 诱导的细胞保护作用被 Akt 和 ERK1/2 抑制剂阻断。结扎大鼠左冠状动脉主干3天或28天，诱发心肌梗死。溴脱氧尿苷（BrdU）标记的MSC在体外用adropin预处理，在缺血后体内心肌内注射，然后静脉注射0.2 mg/kg adropin（双重治疗）。与单独的间充质干细胞移植相比，阿德罗平双重治疗在第3天时血浆中白细胞介素10水平较高，肿瘤坏死因子α和白细胞介素1β水平较低，第28天左心室射血分数和旁分泌因子表达较高，心肌纤维化较少，毛细血管密度较高，并在第3天和第28天产生更多存活的BrdU阳性细胞。 总之，我们的数据证明基于adropin的双重治疗可能会增强间充质干细胞通过旁分泌机制通过促生存途径修复心肌的治疗潜力。
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.
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影响因子：
29
作者：
Kumar KG;Trevaskis JL;Lam DD;Sutton GM;Koza RA;Chouljenko VN;Kousoulas KG;Rogers PM;Kesterson RA;Thearle M;Ferrante AW Jr;Mynatt RL;Burris TP;Dong JZ;Halem HA;Culler MD;Heisler LK;Stephens JM;Butler AA
通讯作者：
Butler AA
影响因子：
9.5
作者：
Fang, Jun;Hu, Fudong;Chen, Lianglong
通讯作者：
Chen, Lianglong
使用干细胞及其衍生的外泌体联合治疗急性心肌梗死可改善心脏性能。
影响因子：
7.5
作者：
Huang, Peisen;Wang, Li;Yang, Yuejin
通讯作者：
Yang, Yuejin
影响因子：
2.7
作者：
Wu, Lingzhen;Fang, Jun;Chen, Lianglong
通讯作者：
Chen, Lianglong
影响因子：
39.3
作者：
Yang, Yue-Jin;Qian, Hai-Yan;Zhao, Shi-Hua
通讯作者：
Zhao, Shi-Hua