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Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379

Oncogenevolume 37pages21372149 (2018) | Download Citation


Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients. A significant reduction in the rate of tumor formation and growth in vivo was observed in T47D breast cancer cells stably expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and protein was also significantly reduced in vitro and in vivo. MSCs were successfully engineered to secrete EVs enriched with miR-379, with the majority found to be of the appropriate size and morphology of exosomal EVs. Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell population, resulted in no adverse effects in vivo. While MSC-379 cells did not impact tumor growth, systemic administration of cell-free EVs enriched with miR-379 was demonstrated to have a therapeutic effect. The data presented support miR-379 as a potent tumor suppressor in breast cancer, mediated in part through regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while engineering the cells to secrete EVs enriched with miR-379 holds exciting potential as an innovative therapy for metastatic breast cancer.

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The authors are grateful to Catherine Curran, Emer Hennessy, Natasha Solovyova, and Dr. Georgina Shaw for technical support provided.


KPO’B and SK: Irish Cancer Society BREAST-PREDICT collaborative cancer research center CCRGAL13; KEG: Irish Research Council (IRC) Postgraduate Scholarship GOIPG/2016/978; HZ: IRC Enterprise Partnership Scheme Postdoctoral Research Fellowship EPSPD/2016/20. JRS and KSJ: Wellcome Trust biomedical vacation scholarship; ADB: Health Research Board summer scholarship SS-2015-1365. This research was also supported by Science Foundation Ireland grants 09/SRC/B1794 and 12/RI/2338, funding from the European Union’s 7th Framework Programme under grant agreement no. HEALTH-2007-B-223298 (PurStem), and the charity Breast Cancer Research.

Author information


  1. Discipline of Surgery, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland

    • K. P. O’Brien
    • , S. Khan
    • , K. E. Gilligan
    • , C. Glynn
    • , A. De Bhulbh
    • , J. R. Schweber
    • , K. St John
    • , M. J. Kerin
    •  & R. M. Dwyer
  2. Cardiovascular Research Centre Galway, School of Medicine, National University of Ireland Galway, Galway, Ireland

    • H. Zafar
  3. Discipline of Anatomy, School of Medicine, National University of Ireland Galway, Galway, Ireland

    • P. Lalor
    •  & P. Dockery
  4. Regenerative Medicine Institute (REMEDI), CURAM, National University of Ireland Galway, Galway, Ireland

    • C. O’Flatharta
    • , J. M. Murphy
    •  & T. O’Brien
  5. Division of Anatomic Pathology, University Hospital Galway, Galway, Ireland

    • H. Ingoldsby
  6. Tissue Optics and Microcirculation Imaging Group, School of Physics, National University of Ireland Galway, Galway, Ireland

    • M. Leahy
  7. Cancer Biology and Therapeutics Laboratory, UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland

    • W. M. Gallagher


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The authors declare that they have no competing interests.

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Correspondence to R. M. Dwyer.

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