Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair
Magnesium lithospermate B enhances the potential of human-induced pluripotent stem cell-derived cardiomyocytes for myocardial repair作者机构：Department of Cardiovascular Surgery The Second Xiangya Hospital Central South University Changsha Hunan China Department of Pharmacology Xiangya School of Pharmaceutical Sciences Central South University Changsha Hunan China Hunan Fangsheng Pharmaceutical Co. Ltd. Changsha Hunan China Department of Thoracic Surgery The Affiliated Cancer Hospital of Xiangya School of Medicine Central South University Changsha Hunan China
出 版 物：《中华医学杂志(英文版)》 (Chinese Medical Journal)
年 卷 期：2024年第137卷第15期
页 面：2024 Jan 15页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was financially supported by the Natural Science Foundation of Hunan Province (Nos. 2023JJ3079 3 2022JJ20088 and 2019JJ50858) the Science and Technology Innovation Program of Hunan Province (No. 2021RC2106) the National Natural Science Foundation of China (No. 82200323) and the Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University
主 题：Myocardial infarction Cell therapy Induced pluripotent stem cells Magnesium lithospermate B Cardiomyocyte Disease modeling hiPSC-CMs
摘 要：Background: We previously reported that activation of the cell cycle in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enhances their remuscularization capacity after human cardiac muscle patch transplantation in infarcted mouse hearts. Herein, we sought to identify the effect of magnesium lithospermate B (MLB) on hiPSC-CMs during myocardial repair using a myocardial infarction (MI) mouse ***: In C57BL/6 mice, MI was surgically induced by ligating the left anterior descending coronary artery. The mice were randomly divided into five groups (n = 10 per group); a MI group (treated with phosphate-buffered saline only), a hiPSC-CMs group, a MLB group, a hiPSC-CMs + MLB group, and a Sham operation group. Cardiac function and MLB therapeutic efficacy were evaluated by echocardiography and histochemical staining 4 weeks after surgery. To identify the associated mechanism, nuclear factor (NF)-κB p65 and intercellular cell adhesion molecule-1 (ICAM1) signals, cell adhesion ability, generation of reactive oxygen species, and rates of apoptosis were detected in human umbilical vein endothelial cells (HUVECs) and ***: After 4 weeks of transplantation, the number of cells that engrafted in the hiPSC-CMs + MLB group was about five times higher than those in the hiPSC-CMs group. Additionally, MLB treatment significantly reduced tohoku hospital pediatrics-1 (THP-1) cell adhesion, ICAM1 expression, NF-κB nuclear translocation, reactive oxygen species production, NF-κB p65 phosphorylation, and cell apoptosis in HUVECs cultured under hypoxia. Similarly, treatment with MLB significantly inhibited the apoptosis of hiPSC-CMsvia enhancing signal transducer and activator of transcription 3 (STAT3) phosphorylation and B-cell lymphoma-2 (BCL2) expression, promoting STAT3 nuclear translocation, and downregulating BCL2-Associated X, dual specificity phosphatase 2 (DUSP2), and cleaved-caspase-3 expression under hypoxia. Furthermore, MLB significan
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