[1]钟剑锋,王杰鑫,李上海,等.单核巨噬细胞膜修饰iPSC-CM来源外泌体靶向修复损伤心脏的实验研究[J].医学信息,2023,36(17):76-82.[doi:10.3969/j.issn.1006-1959.2023.17.014]
 ZHONG Jian-feng,WANG Jie-xin,LI Shang-hai,et al.Experimental Study on Targeted Repair of Injured Heart by iPSC-CM-derived Exosomes Modified by Monocyte-macrophage Membrane[J].Journal of Medical Information,2023,36(17):76-82.[doi:10.3969/j.issn.1006-1959.2023.17.014]
点击复制

单核巨噬细胞膜修饰iPSC-CM来源外泌体靶向修复损伤心脏的实验研究()
分享到:

医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
36卷
期数:
2023年17期
页码:
76-82
栏目:
论著
出版日期:
2023-09-01

文章信息/Info

Title:
Experimental Study on Targeted Repair of Injured Heart by iPSC-CM-derived Exosomes Modified by Monocyte-macrophage Membrane
文章编号:
1006-1959(2023)17-0076-07
作者:
钟剑锋王杰鑫李上海
(广东医科大学附属医院心内科,广东 湛江 524001)
Author(s):
ZHONG Jian-fengWANG Jie-xinLI Shang-haiet al.
(Department of Cardiology,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,Guangdong,China)
关键词:
心肌梗死iPSC-CMs外泌体靶向治疗
Keywords:
Myocardial infarctioniPSC-CMsExosomesTargeted therapy
分类号:
R541.4;R459.9
DOI:
10.3969/j.issn.1006-1959.2023.17.014
文献标志码:
A
摘要:
目的 利用单核巨噬细胞膜修饰人多潜能干细胞诱导心肌细胞(iPSC-CMs)来源的外泌体并探讨其心肌修复作用。方法 使用高速离心法提取iPSC-CMs来源的外泌体,试剂盒提取单核巨噬细胞膜。采用脂质体挤出器融合外泌体和细胞膜,Western blot、透射电镜和纳米颗粒分析仪评价膜融合效果。采用CCK-8试验检测细胞活力,建立小鼠心肌梗死模型,隔天静脉注射M-iCM-EXs(1011个EXs/kg)3次;6 h后采用小动物活体光学成像系统评价M-iCM-EXs对损伤心脏的靶向性;28 d后采用Masson三色染色评估M-iCM-EXs治疗对心肌梗死后心室重构的作用和心动超声图评价M-iCM-EXs治疗后对的心功能变化。结果 CCK-8试验证实M-iCM-EXs可提高OGD后细胞活力;小动物活体光学成像系统证实M-iCM-EXs对损伤心脏具有靶向性;Masson染色和心动超声图证实M-iCM-EXs治疗后能抑制小鼠心肌梗死后的心室重塑。结论 单核巨噬细胞膜修饰iPSC-CM来源的外泌体具有靶向损伤心肌的能力,能更有效修复损伤心脏。
Abstract:
Objective To study and explore its myocardial repair effect.Methods The exosomes derived from iPSC-CMs were extracted by high-speed centrifugation, and the mononuclear macrophage membrane was extracted by the kit. The exosomes and cell membranes were fused by liposome extruder, and the membrane fusion effect was evaluated by Western blot, transmission electron microscopy and nanoparticle analyzer. CCK-8 assay was used to detect cell viability, and a mouse model of myocardial infarction was established. M-iCM-EXs (1011 EXs/kg) was intravenously injected every other day for 3 times. After 6 h, the targeting of M-iCM-EXs to injured heart was evaluated by small animal in vivo optical imaging system. After 28 days, Masson trichrome staining was used to evaluate the effect of M-iCM-EXs treatment on ventricular remodeling after myocardial infarction and echocardiography was used to evaluate the changes of cardiac function after M-iCM-EXs treatment.Results CCK-8 assay confirmed that M-iCM-EXs could improve cell viability after OGD. Small animal imaging technology confirmed the targeting of M-iCM-EXs to ischemic myocardial tissue. Masson trichrome staining test and echocardiography confirmed that M-iCM-EXs treatment could inhibit ventricular remodeling and improve cardiac function after MI in mice.Conclusion The iPSC-CMs-derived exosomes modified by monocyte-macrophage membrane have the ability to target damaged myocardium and can repair damaged heart more effectively.

参考文献/References:

[1]急性ST段抬高型心肌梗死诊断和治疗指南(2019)[J].中华心血管病杂志,2019(10):766-783.[2]Gao L,Wang L,Wei Y,et al.Exosomes secreted by hiPSC-derived cardiac cells improve recovery from myocardial infarction in swine[J].Sci Transl Med,2020,12(561):eaay1318.[3]Heallen TR,Martin JF.Heart repair via cardiomyocyte-secreted vesicles[J].Nat Biomed Eng,2018,2(5):271-272.[4]Zhao H,Chen X,Hu G,et al.Small Extracellular Vesicles From Brown Adipose Tissue Mediate Exercise Cardioprotection[J].Circ Res,2022,130(10):1490-1506.[5]Zhang N,Song Y,Huang Z,et al.Monocyte mimics improve mesenchymal stem cell-derived extracellular vesicle homing in a mouse MI/RI model[J].Biomaterials,2020,255:120168.[6]刘马超,杭莺,刘云,等.白细胞计数、中性粒细胞与淋巴细胞比值对急性心肌梗死患者短期预后的影响分析[J].中国心血管杂志,2018,23(5):384-388.[7]路阳,赵宁,杜以梅.单核巨噬细胞在心肌炎中的作用[J].中国心血管杂志,2021,26(4):402-405.[8]Huang CK,Dai D,Xie H,et al.Lgr4 Governs a Pro-Inflammatory Program in Macrophages to Antagonize Post-Infarction Cardiac Repair[J].Circ Res,2020,127(8):953-973.[9]Ye L,Chang YH,Xiong Q,et al.Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells[J].Cell Stem Cell,2014,15(6):750-761.[10]Tan SH,Loo SJ,Gao Y,et al.Thymosin β4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction[J].Theranostics,2021,11(16):7879-7895.[11]Paik DT,Tian L,Lee J,et al.Large-Scale Single-Cell RNA-Seq Reveals Molecular Signatures of Heterogeneous Populations of Human Induced Pluripotent Stem Cell-Derived Endothelial Cells[J].Circ Res,2018,123(4):443-450.[12]Adamiak M,Cheng G,Bobis-Wozowicz S,et al.Induced Pluripotent Stem Cell (iPSC)-Derived Extracellular Vesicles Are Safer and More Effective for Cardiac Repair Than iPSCs[J].Circ Res,2018,122(2):296-309.[13]El Harane N,Kervadec A,Bellamy V,et al.Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors[J].Eur Heart J,2018,39(20):1835-1847. [14]Smyth T,Kullberg M,Malik N,et al.Biodistribution and delivery efficiency of unmodified tumor-derived exosomes[J].J Control Release,2015,199:145-155.[15]Elkhoury K,Chen M,Ko?觭ak P,et al.Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA[J].Biofabrication,2022,14(4):10.1088/1758-5090/ac8621.[16]Liu B,Lee BW,Nakanishi K,et al.Cardiac recovery via extended cell-free delivery of extracellular vesicles secreted by cardiomyocytes derived from induced pluripotent stem cells[J].Nat Biomed Eng,2018,2(5):293-303.[17]Belhadj Z,He B,Deng H,et al.A combined "eat me/don’t eat me" strategy based on extracellular vesicles for anticancer nanomedicine[J].J Extracell Vesicles,2020,9(1):1806444.[18]Advani R,Flinn I,Popplewell L,et al.CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma[J].N Engl J Med,2018,379(18):1711-1721.[19]Morrissey MA,Kern N,Vale RD.CD47 Ligation Repositions the Inhibitory Receptor SIRPA to Suppress Integrin Activation and Phagocytosis[J].Immunity,2020,53(2):290-302.e6.[20]Niessen HW,Lagrand WK,Visser CA,et al.Upregulation of ICAM-1 on cardiomyocytes in jeopardized human myocardium during infarction[J].Cardiovasc Res,1999,41(3):603-610.[21]Xie L,Galettis A,Morris J,et al.Intercellular adhesion molecule-1 (ICAM-1) expression is necessary for monocyte adhesion to the placental bed endothelium and is increased in type 1 diabetic human pregnancy [J].Diabetes Metab Res Rev,2008,24(4):294-300.[22]Vandergriff A,Huang K,Shen D,et al.Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide[J].Theranostics,2018,8(7):1869-1878.[23]Wang X,Chen Y,Zhao Z,et al.Engineered Exosomes With Ischemic Myocardium-Targeting Peptide for Targeted Therapy in Myocardial Infarction[J].J Am Heart Assoc,2018,7(15):e008737.[24]De La Pe?觡a H,Madrigal JA,Rusakiewicz S,et al.Artificial exosomes as tools for basic and clinical immunology[J].J Immunol Methods,2009,344(2):121-132.[25]Gao X,Ran N,Dong X,et al.Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy[J].Sci Transl Med,2018,10(444):eaat0195.[26]Hu S,Wang X,Li Z,et al.Platelet membrane and stem cell exosome hybrid enhances cellular uptake and targeting to heart injury[J].Nano Today,2021,39:101210.

相似文献/References:

[1]冯 湧.新一代抗凝血药阿加曲班的临床应用进展[J].医学信息,2018,31(02):43.[doi:10.3969/j.issn.1006-1959.2018.02.015]
 FENG Yong.Progress in Clinical Application of the New Generation Anticoagulant Agatripine[J].Journal of Medical Information,2018,31(17):43.[doi:10.3969/j.issn.1006-1959.2018.02.015]
[2]翟公伟,赵培华,滑 艳.30岁以下急性ST段抬高型心肌梗死患者临床特点分析[J].医学信息,2018,31(05):81.[doi:10.3969/j.issn.1006-1959.2018.05.026]
 ZHAI Gong-wei,ZHAO Pei-hua,HUA Yan.Clinical Characteristics of Acute ST-segment Elevation Myocardial Infarction under 30 Years of Age[J].Journal of Medical Information,2018,31(17):81.[doi:10.3969/j.issn.1006-1959.2018.05.026]
[3]杜浩珲.溶栓后PCI与pPCI治疗急性ST段抬高型心肌梗死的 临床效果研究[J].医学信息,2018,31(08):69.[doi:10.3969/j.issn.1006-1959.2018.08.021]
 DU Hao-hun.Clinical Effect of PCI and pPCI on Acute ST Segment Elevation Myocardial Infarction after Thrombolysis[J].Journal of Medical Information,2018,31(17):69.[doi:10.3969/j.issn.1006-1959.2018.08.021]
[4]宋俊燕,张 毅.重组人尿激酶原在急性ST段抬高型心肌梗死中的 疗效及并发症分析[J].医学信息,2018,31(11):133.[doi:10.3969/j.issn.1006-1959.2018.11.042]
 SONG Jun-yan,ZHANG Yi.Therapeutic Efficacy and Complications of Recombinant Human Pro-urokinase in Acute ST-elevation Myocardial Infarction[J].Journal of Medical Information,2018,31(17):133.[doi:10.3969/j.issn.1006-1959.2018.11.042]
[5]李素军.早期心脏康复运动治疗方案对急性非ST段抬高 心肌梗死的效果观察[J].医学信息,2018,31(15):89.[doi:10.3969/j.issn.1006-1959.2018.15.027]
 LI Su-jun.Effect of Early Cardiac Rehabilitation Exercise on Acute Non-ST-Elevation Myocardial Infarction[J].Journal of Medical Information,2018,31(17):89.[doi:10.3969/j.issn.1006-1959.2018.15.027]
[6]金 鹏,周炳凤.去甲肾上腺素在心肌梗死合并低血压中的应用[J].医学信息,2020,33(07):57.[doi:10.3969/j.issn.1006-1959.2020.07.017]
 JIN Peng,ZHOU Bing-feng.Application of Norepinephrine in Myocardial Infarction with Hypotension[J].Journal of Medical Information,2020,33(17):57.[doi:10.3969/j.issn.1006-1959.2020.07.017]
[7]朱贝利,刘 辉,耿硕章,等.心肌梗死后缺血性心肌病心衰患者血浆半乳糖凝集素3的表达及其临床意义[J].医学信息,2020,33(15):61.[doi:10.3969/j.issn.1006-1959.2020.15.020]
 ZHU Bei-li,LIU Hui,GENG Shuo-zhang,et al.Expression of Plasma Galectin-3 in Patients with Ischemic Cardiomyopathy and Heart Failure After Myocardial Infarction and Its Clinical Significance[J].Journal of Medical Information,2020,33(17):61.[doi:10.3969/j.issn.1006-1959.2020.15.020]
[8]张 宁,孙经武,刘 振,等.鸢尾素与心血管疾病的相关性[J].医学信息,2021,34(02):56.[doi:10.3969/j.issn.1006-1959.2021.02.016]
 ZHANG Ning,SUN Jing-wu,LIU Zhen,et al.Study on the Correlation Between Irisin and Cardiovascular Disease[J].Journal of Medical Information,2021,34(17):56.[doi:10.3969/j.issn.1006-1959.2021.02.016]
[9]邓 伟.冠脉无复流的危险因素及治疗[J].医学信息,2021,34(03):43.[doi:10.3969/j.issn.1006-1959.2021.03.013]
 DENG Wei.Risk Factors and Treatment of No-reflow of Coronary Artery[J].Journal of Medical Information,2021,34(17):43.[doi:10.3969/j.issn.1006-1959.2021.03.013]
[10]苏长阳,帅东东,王 磊,等.硝普钠联合多巴胺治疗心肌梗死后左心衰竭的疗效[J].医学信息,2021,34(03):157.[doi:10.3969/j.issn.1006-1959.2021.03.044]
 SU Chang-yang,SHUAI Dong-dong,WANG Lei,et al.Efficacy of Sodium Nitroprusside Combined with Dopamine in the Treatment of Left Heart Failure After Myocardial Infarction[J].Journal of Medical Information,2021,34(17):157.[doi:10.3969/j.issn.1006-1959.2021.03.044]

更新日期/Last Update: 1900-01-01