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Translational Stroke Research

, Volume 10, Issue 5, pp 509–521 | Cite as

Application of Mesenchymal Stem Cell-Derived Extracellular Vesicles for Stroke: Biodistribution and MicroRNA Study

  • Gyeong Joon Moon
  • Ji Hee Sung
  • Dong Hee Kim
  • Eun Hee Kim
  • Yeon Hee Cho
  • Jeong Pyo Son
  • Jae Min Cha
  • Oh Young BangEmail author
Original Article

Abstract

Mesenchymal stem cells (MSCs) exert their therapeutic capability through a variety of bioactive substances, including trophic factors, microRNAs, and extracellular vesicles (EVs) in infarcted tissues. We therefore hypothesized that MSC-derived EVs (MSC-EVs) possess therapeutic molecules similar to MSCs. Moreover, given their nature as nanosized and lipid-shielded particles, the intravenous infusion of MSC-EVs would be advantageous over MSCs as a safer therapeutic approach. In this study, we investigated the biodistribution, therapeutic efficacy, and mode of action of MSC-EVs in a rat stroke model. MSC-EVs successfully stimulated neurogenesis and angiogenesis in vivo. When compared to the MSC-treated group, rats treated with MSC-EVs exhibited greater behavioral improvements than the control group (p < 0.05). Our biodistribution study using fluorescence-labeled MSC-EVs and MSCs demonstrated that the amounts of MSC-EVs in the infarcted hemisphere increased in a dose-dependent manner, and were rarely found in the lung and liver. In addition, MSC-EVs were highly inclusive of various proteins and microRNAs (miRNAs) associated with neurogenesis and/or angiogenesis compared to fibro-EVs. We further analyzed those miRNAs and found that miRNA-184 and miRNA-210 were essential for promoting neurogenesis and angiogenesis of MSC-EVs, respectively. MSC-EVs represent an ideal alternative to MSCs for stroke treatment, with similar medicinal capacity but an improved safety profile that overcomes cell-associated limitations in stem cell therapy.

Keywords

Stroke Mesenchymal stem cells Extracellular vesicles Neurogenesis Angiogenesis MicroRNAs 

Notes

Authors’ Contributions

G.J.M.: conception and design, manuscript writing, financial support, collection and/or assembly of data, data analysis and interpretation, administrative support, final approval of manuscript; J.H.S.: provision of study material, collection and/or assembly of data, data analysis and interpretation; D.H.K.: collection and/or assembly of data, data analysis and interpretation, provision of study material; E.H.K.: collection and/or assembly of data, data analysis and interpretation, provision of study material; Y.H.C.: collection and/or assembly of data, data analysis and interpretation, provision of study material; J.P.S.: collection and/or assembly of data, data analysis and interpretation, provision of study material; J.M.C.: collection and/or assembly of data, provision of study material; O.Y.B.: conception and design, financial support, final approval of manuscript.

Funding

This study was supported by a grant from the Korean Healthcare Technology R&D Project, Ministry of Health & Welfare (HI14C1439, HI14C3484, HI17C1256) and Basic Science Research Program, the Ministry of Science, ICT and Future Planning (NRF-2013R1A1A2058139 and NRF-2014R1A1A1004645).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All animal experiments were approved by the Institutional Animal Care and Use Committee (IACUC) of Samsung Biomedical Research Institute (SBRI, Approval No. 20140203001) and performed in accordance with the Institute of Laboratory Animal Resources (ILAR) guide. All animals were maintained in compliance with the relevant laws and institutional guidelines of the Laboratory Animal Research Center (LARC; AAALAC International approved facility, No. 001003) at the Samsung Medical Center.

Supplementary material

12975_2018_668_MOESM1_ESM.pdf (1.1 mb)
ESM 1 (PDF 1143 kb)
12975_2018_668_MOESM2_ESM.wmv (1.7 mb)
ESM 2 (WMV 1713 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Gyeong Joon Moon
    • 1
    • 2
  • Ji Hee Sung
    • 1
    • 3
  • Dong Hee Kim
    • 1
    • 3
    • 4
  • Eun Hee Kim
    • 1
    • 3
  • Yeon Hee Cho
    • 1
    • 3
  • Jeong Pyo Son
    • 1
    • 4
  • Jae Min Cha
    • 5
  • Oh Young Bang
    • 1
    • 3
    • 4
    • 6
    Email author
  1. 1.Translational and Stem Cell Research Laboratory on Stroke, School of MedicineSungkyunkwan UniversitySeoulSouth Korea
  2. 2.School of Life Sciences, BK21 plus KNU Creative BioResearch GroupKyungpook National UniversityDaeguSouth Korea
  3. 3.Stem Cell & Regenerative Medicine Institute for Future MedicineSamsung Medical CenterSeoulSouth Korea
  4. 4.Samsung Advanced Institute for Health Sciences and TechnologySungkyunkwan UniversitySeoulSouth Korea
  5. 5.3D Stem Cell Bioprocessing Laboratory, Department of MechatronicsIncheon National UniversityIncheonRepublic of Korea
  6. 6.Department of Neurology, Samsung Medical Center, School of MedicineSungkyunkwan UniversitySeoulSouth Korea

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