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Journal of Molecular Medicine

, Volume 92, Issue 4, pp 387–397 | Cite as

Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model

  • Suyan Bian
  • Liping ZhangEmail author
  • Liufa Duan
  • Xi Wang
  • Ying Min
  • Hepeng Yu
Original Article

Abstract

Mesenchymal stem cells (MSCs) have been increasingly tested experimentally and clinically for cardiac repair. However, the underlying mechanisms remain controversial due to the poor viability and considerable death of the engrafted cells in the infracted myocardium. Recent reports have suggested that extracellular vesicles (EVs) released by MSCs have angiogenesis-promoting activity; however, the therapeutic effect of MSC-EVs on an ischemic heart is unclear. In the present study, we reported that MSCs could release a large quantity of EVs around 100 nm in diameter upon hypoxia stimulation though the majority of the cells had not experienced apoptosis. MSC-EVs could be promptly uptaken by human umbilical vein endothelial cells, and the internalization resulted in dose-dependent enhancement of in vitro proliferation, migration, and tube formation of endothelial cells. Using an acute myocardial infarction rat model, we found that intramyocardial injection of MSC-EVs markedly enhanced blood flow recovery, in accordance with reduced infarct size and preserved cardiac systolic and diastolic performance compared to those treated with PBS. These data suggest that like MSCs, MSC-EVs could also protect cardiac tissue from ischemic injury at least by means of promoting blood vessel formation, though further detailed investigations should be performed to define the functionality of MSC-EVs.

Key messages

  • MSCs released extracellular vesicles (EVs) upon hypoxia stimulation.

  • MSC-EVs were a mixture of microvesicles and exosomes.

  • MSC-EVs could be promptly uptaken by human umbilical vein endothelial cells.

  • MSC-EVs promoted neoangiogenesis in vitro and in vivo.

  • MSC-EVs preserved cardiac performance in an AMI model.

Keywords

Human bone marrow mesenchymal stem cells Human umbilical vein endothelial cells Extracellular vesicles Angiogenesis Myocardial infarction 

Notes

Acknowledgments

This work was supported by the National Natural Science Funds for Youth (no. 81100107, to Bian Suyan). We thank Professor Zikuan Guo for providing the human bone marrow MSCs and the HUVEC cells and critical review of this manuscript.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Suyan Bian
    • 1
  • Liping Zhang
    • 1
    Email author
  • Liufa Duan
    • 1
  • Xi Wang
    • 1
  • Ying Min
    • 1
  • Hepeng Yu
    • 1
  1. 1.The Second Department of Geriatric CardiologyChinese PLA General HospitalBeijingChina

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