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从早期妊娠获得的人蜕膜间充质干细胞通过激活鸟氨酸代谢改善心肌梗死后的心脏血管再生。

Human Decidual Mesenchymal Stem Cells Obtained From Early Pregnancy Improve Cardiac Revascularization Postinfarction by Activating Ornithine Metabolism.

作者信息

Chen Kegong, Bai Long, Lu Jingtong, Chen Wei, Liu Chang, Guo Erliang, Qin Xionghai, Jiao Xuan, Huang Mingli, Tian Hai

机构信息

Department of Cardiovascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, China.

出版信息

Front Cardiovasc Med. 2022 Feb 11;9:837780. doi: 10.3389/fcvm.2022.837780. eCollection 2022.

Abstract

BACKGROUND

Compared with bone marrow mesenchymal stem cells (BMSCs), decidual mesenchymal stem cells (DMSCs) are easy to obtain and exhibit excellent angiogenic effects, but their role in cell transplantation after myocardial infarction (MI) remains unclear.

METHODS

BMSCs and DMSCs were harvested from healthy donors. The effects of both cell types on angiogenesis were observed . Metabonomics analysis was performed to compare different metabolites and screen critical metabolic pathways. A murine model of acute myocardial infarction (AMI) was established, which was randomized into five groups (control, BMSC, DMSC, DMSC + ODCshRNA and BMSC + ODC consisting of 50 animals, equally divided into each group). The therapeutic effect of DMSCs on MI in rats was assessed based on neovascularization and cardiac remodeling.

RESULTS

DMSCs exhibited a better angiogenic effect on human umbilical vein endothelial cells (HUVECs) than BMSCs . In addition, ornithine metabolism, which is associated with vascularization, was significantly increased in DMSCs. The transplantation of DMSCs in the rat MI model significantly enhanced angiogenesis of the infarct border area and improved cardiac remodeling and dysfunction postinfarction compared with BMSCs. Furthermore, inhibition of ornithine metabolism by silencing ornithine decarboxylase (ODC) in DMSCs partly abolished the benefits of DMSC transplantation.

CONCLUSION

Compared with BMSCs, DMSCs exhibited better efficacy in improving revascularization and heart remodeling post-MI via the activation of ODC-associated ornithine metabolism.

摘要

背景

与骨髓间充质干细胞(BMSCs)相比,蜕膜间充质干细胞(DMSCs)易于获取且具有出色的血管生成作用,但其在心肌梗死(MI)后细胞移植中的作用仍不清楚。

方法

从健康供体中获取BMSCs和DMSCs。观察两种细胞类型对血管生成的影响。进行代谢组学分析以比较不同代谢物并筛选关键代谢途径。建立急性心肌梗死(AMI)小鼠模型,将其随机分为五组(对照组、BMSC组、DMSC组、DMSC + ODCshRNA组和BMSC + ODC组,每组50只动物,每组动物数量均等)。基于新生血管形成和心脏重塑评估DMSCs对大鼠MI的治疗效果。

结果

与BMSCs相比,DMSCs对人脐静脉内皮细胞(HUVECs)表现出更好的血管生成作用。此外,与血管生成相关的鸟氨酸代谢在DMSCs中显著增加。与BMSCs相比,在大鼠MI模型中移植DMSCs可显著增强梗死边缘区域的血管生成,并改善梗死后的心脏重塑和功能障碍。此外,通过沉默DMSCs中的鸟氨酸脱羧酶(ODC)抑制鸟氨酸代谢,部分消除了DMSC移植的益处。

结论

与BMSCs相比,DMSCs通过激活与ODC相关的鸟氨酸代谢,在改善MI后的血管再通和心脏重塑方面表现出更好的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ade3/8887417/377bb1f0a166/fcvm-09-837780-g0006.jpg

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