Human peripheral blood‑derived exosomes for microRNA delivery

Kang,Ji‑Young; Park,Hyewon; Kim,Hyoeun; Mun,Dasom; Park,Hyelim; Yun,Nuri; Joung,Boyoung

doi:10.3892/ijmm.2019.4150

Human peripheral blood‑derived exosomes for microRNA delivery

Authors:
- Ji‑Young Kang
- Hyewon Park
- Hyoeun Kim
- Dasom Mun
- Hyelim Park
- Nuri Yun
- Boyoung Joung
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Affiliations: Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea, Institute of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
Published online on: March 28, 2019 https://doi.org/10.3892/ijmm.2019.4150
Pages: 2319-2328
Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exosomes serve important functions in cell‑to‑cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood‑derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR‑21 using a human peripheral blood derived‑exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL‑1 cells, miR‑21 expression was successfully regulated by treatment with human peripheral blood derived‑exosomes loaded with an miR‑21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor‑loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR‑21 mimic‑ or inhibitor‑loaded exosomes. Furthermore, miR‑21 mimic‑loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA‑loaded human peripheral blood derived‑exosomes may be used as a therapeutic tool for cardiac diseases.

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