Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease asso...Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.展开更多
Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect simila...Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.展开更多
目的系统性评价干细胞来源外泌体治疗大鼠心肌梗死的有效性。方法检索PubMed和中国生物医学文献服务系统(SinoMed)等数据库,采用主题词方式进行检索,外文数据库以Pubmed为例,检索策略为:exosomes AND stem cells AND myocardial infarct...目的系统性评价干细胞来源外泌体治疗大鼠心肌梗死的有效性。方法检索PubMed和中国生物医学文献服务系统(SinoMed)等数据库,采用主题词方式进行检索,外文数据库以Pubmed为例,检索策略为:exosomes AND stem cells AND myocardial infarction;中文数据库以中国生物医学文献服务系统(SinoMed)为例,检索策略为:((外泌体)AND(干细胞))AND(心肌梗死);收集干细胞来源外泌体治疗大鼠心肌梗死模型的相关文献并最终纳入10篇文献进行Meta分析。首先行异质性检验,然后逐次剔除单个研究,进行敏感性分析,最后漏斗图检测文章发表偏倚。结果最终纳入10篇动物实验文献,共179只大鼠。实验组97只采用干细胞来源的外泌体治疗,对照组82只采取空白对照、生理盐水或者PBS干预。Meta分析结果示:干细胞来源的外泌体治疗可以显著提高心肌梗死大鼠的左室射血分数(SMD=13.91,95%CI:8.90~18.91,P<0.01)、左室短轴收缩率(SMD=7.52,95%CI:5.29~9.76,P<0.01)以及减少心梗面积(SMD=−15.15,95%CI:−17.90~−12.40,P<0.01)。结论干细胞来源的外泌体治疗可明显改善心肌梗死大鼠的心功能。展开更多
基金Supported by Research grant,No.103544/2016-PLaqueIMAGE,contract No.26/01.09.2016financed by the Romanian Ministry of European Funds,the Romanian Government and the European Union
文摘Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.
基金supported by grants from the National Natural Science Foundation of China(No.81971765,31771060,31671025,81871504,32171355 and 82172103).
文摘Currently,stem cell transplantations in cardiac repair are limited owing to disadvantages,such as immunological rejection and poor cell viability.Although direct injection of exosomes can have a curative effect similar to that of stem cell transplantation,high clearance hinders its application in clinical practice.Previous reports suggested that induction of coronary collateralization can be a desired method of adjunctive therapy for someone who had missed the optimal operation time to attenuate myocardial ischemia.In this study,to mimic the paracrine and biological activity of stem cells,we developed artificial stem cells that can continuously release Tβ4-exosomes(Tβ4-ASCs)by encapsulating specific exosomes within microspheres using microfluidics technology.The results show that Tβ4-ASCs can greatly promote coronary collateralization in the periphery of the myocardial infarcted area,and its therapeutic effect is superior to that of directly injecting the exosomes.In addition,to better understand how it works,we demonstrated that the Tβ4-ASC-derived exosomes can enhance the angiogenic capacity of coronary endothelial cells(CAECs)via the miR-17-5p/PHD3/Hif-1αpathway.In brief,as artificial stem cells,Tβ4-ASCs can constantly release functional exosomes and stimulate the formation of collateral circulation after myocardial infarction,providing a feasible and alternative method for clinical revascularization.
文摘目的系统性评价干细胞来源外泌体治疗大鼠心肌梗死的有效性。方法检索PubMed和中国生物医学文献服务系统(SinoMed)等数据库,采用主题词方式进行检索,外文数据库以Pubmed为例,检索策略为:exosomes AND stem cells AND myocardial infarction;中文数据库以中国生物医学文献服务系统(SinoMed)为例,检索策略为:((外泌体)AND(干细胞))AND(心肌梗死);收集干细胞来源外泌体治疗大鼠心肌梗死模型的相关文献并最终纳入10篇文献进行Meta分析。首先行异质性检验,然后逐次剔除单个研究,进行敏感性分析,最后漏斗图检测文章发表偏倚。结果最终纳入10篇动物实验文献,共179只大鼠。实验组97只采用干细胞来源的外泌体治疗,对照组82只采取空白对照、生理盐水或者PBS干预。Meta分析结果示:干细胞来源的外泌体治疗可以显著提高心肌梗死大鼠的左室射血分数(SMD=13.91,95%CI:8.90~18.91,P<0.01)、左室短轴收缩率(SMD=7.52,95%CI:5.29~9.76,P<0.01)以及减少心梗面积(SMD=−15.15,95%CI:−17.90~−12.40,P<0.01)。结论干细胞来源的外泌体治疗可明显改善心肌梗死大鼠的心功能。
