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Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22.

Feng Y, Huang W, Wani M, Yu X, Ashraf M - PLoS ONE (2014)

Bottom Line: Furthermore, the anti-apoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2).In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis.Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Cardiovascular Institute, Southern Medical University, Guangzhou, China ; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.

ABSTRACT
Mesenchymal stem cells (MSCs) have potential application for the treatment of ischemic heart diseases. Besides differentiation properties, MSCs protect ischemic cardiomyocytes by secretion of paracrine factors. In this study, we found exosomes enriched with miR-22 were secreted by MSCs following ischemic preconditioning (Exo(IPC)) and mobilized to cardiomyocytes where they reduced their apoptosis due to ischemia. Interestingly, by time-lapse imaging, we for the first time captured the dynamic shedding of miR-22 loaded exosomes from cytosol to extracellular space. Furthermore, the anti-apoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2). In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis. Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.

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Related in: MedlinePlus

Time-lapse imaging for the transfer of exosomal miR-22.A. Flow chart of time-lapse confocal imaging experiment. B. Live cell imaging of MSCs co-transfected with lentivirus overexpressing fusion protein CD63-RFP (red) and miR-22 labeled with fluorescein (green).
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pone-0088685-g003: Time-lapse imaging for the transfer of exosomal miR-22.A. Flow chart of time-lapse confocal imaging experiment. B. Live cell imaging of MSCs co-transfected with lentivirus overexpressing fusion protein CD63-RFP (red) and miR-22 labeled with fluorescein (green).

Mentions: In order to capture the dynamic shedding of miR-22 from MSC, we employed time-lapse confocal imaging. First, we transduced lentivirus pCT-CD63-RFP in MSCs to label exosomes by overexpressing the fusion protein CD63-RFP. Then we transfected fluorescein labeled miR-22. Colocalization of red fusion protein CD63-RFP and green miR-22 indicated that miR-22 transferred to exosomes (Fig. 3A). Very interestingly, we captured the dynamic shedding course of miR-22 loaded exosomes from cytosol into extracellular space (Fig. 3B and Video S1). This is the first report to visualize microRNA shedding via exosomes.


Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22.

Feng Y, Huang W, Wani M, Yu X, Ashraf M - PLoS ONE (2014)

Time-lapse imaging for the transfer of exosomal miR-22.A. Flow chart of time-lapse confocal imaging experiment. B. Live cell imaging of MSCs co-transfected with lentivirus overexpressing fusion protein CD63-RFP (red) and miR-22 labeled with fluorescein (green).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928277&req=5

pone-0088685-g003: Time-lapse imaging for the transfer of exosomal miR-22.A. Flow chart of time-lapse confocal imaging experiment. B. Live cell imaging of MSCs co-transfected with lentivirus overexpressing fusion protein CD63-RFP (red) and miR-22 labeled with fluorescein (green).
Mentions: In order to capture the dynamic shedding of miR-22 from MSC, we employed time-lapse confocal imaging. First, we transduced lentivirus pCT-CD63-RFP in MSCs to label exosomes by overexpressing the fusion protein CD63-RFP. Then we transfected fluorescein labeled miR-22. Colocalization of red fusion protein CD63-RFP and green miR-22 indicated that miR-22 transferred to exosomes (Fig. 3A). Very interestingly, we captured the dynamic shedding course of miR-22 loaded exosomes from cytosol into extracellular space (Fig. 3B and Video S1). This is the first report to visualize microRNA shedding via exosomes.

Bottom Line: Furthermore, the anti-apoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2).In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis.Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Cardiovascular Institute, Southern Medical University, Guangzhou, China ; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.

ABSTRACT
Mesenchymal stem cells (MSCs) have potential application for the treatment of ischemic heart diseases. Besides differentiation properties, MSCs protect ischemic cardiomyocytes by secretion of paracrine factors. In this study, we found exosomes enriched with miR-22 were secreted by MSCs following ischemic preconditioning (Exo(IPC)) and mobilized to cardiomyocytes where they reduced their apoptosis due to ischemia. Interestingly, by time-lapse imaging, we for the first time captured the dynamic shedding of miR-22 loaded exosomes from cytosol to extracellular space. Furthermore, the anti-apoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2). In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis. Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.

Show MeSH
Related in: MedlinePlus