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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.01225

Extracellular Vesicles Can Deliver Anti-Inflammatory and Anti-Scarring Activities of Mesenchymal Stromal Cells after Spinal Cord Injury.

 Pasquale Romanelli1, 2,  Lara Bieler1, 2, Cornelia Scharler2, 3, Karin Pachler2, 4,  Christina Kreutzer1, 2,  Pia Zaunmair1, 2, Dominika Jakubecova4,  Heike Mrowetz2, 5, Bruno Benedetti1, 2,  Francisco J. Rivera2, 5, 6, 7,  Ludwig Aigner2, 5, 8,  Eva Rohde2, 4, 9,  Mario Gimona2, 4,  Dirk Strunk3, 4 and  Sebastien Couillard-Despres1, 2, 8*
  • 1Institute of Experimental Neuroregeneration, Paracelsus Medical University, Austria
  • 2Spinal Cord Injury and Tissue Regeneration Center Salzburg, Austria
  • 3Institute for Experimental and Clinical Cell Therapy, Paracelsus Medical University, Austria
  • 4Paracelsus Medical University, Austria
  • 5Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Austria
  • 6Laboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Austral University of Chile, Chile
  • 7Center for Interdisciplinary Studies on the Nervous System, Faculty of Medicine, Austral University of Chile, Chile
  • 8Austrian Cluster for Tissue Regeneration, Austria
  • 9Department of Transfusion Medicine, University Hospital Salzburg, Austria

Spinal cord injury is characterized by an initial neural tissue disruption triggering secondary damage and extensive non-resolving inflammation, which aggravates loss of function and hinders recovery. The early onset of inflammation following traumatic spinal cord injury underscores the importance of acute intervention after the initial trauma. Injections of mesenchymal stromal cells (MSCs) can reduce inflammation following spinal cord injury. We asked if extracellular vesicles (EVs) can substitute anti-inflammatory and anti-scarring activities of their parental MSCs in a rat model of contusion spinal cord injury. We report that MSC-EVs were as potent as the parental intact cells in reducing the level of neuroinflammation for up to two weeks post-injury. Acute application of EVs after spinal cord injury was shown to robustly decrease the expression of pro-inflammatory cytokines in the spinal cord parenchyma in the very early phase of secondary damage. Moreover, the anti-scarring impact of MSC-EVs was even more efficient than the parental cells. We therefore conclude that anti-inflammatory and anti-scarring activities of MSCs application can be mediated by their secreted EVs. In light of their substantial safety and druggability advantages, EVs may have a high potential as early therapeutic following traumatic spinal cord injury.

Keywords: exosome (vesicle), Inflammation, Scarring, spinal cord injury (SCI), Mesenchymal stroma cells

Received: 04 Jun 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Romanelli, Bieler, Scharler, Pachler, Kreutzer, Zaunmair, Jakubecova, Mrowetz, Benedetti, Rivera, Aigner, Rohde, Gimona, Strunk and Couillard-Despres. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Sebastien Couillard-Despres, Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Salzburg, Austria,