Extracellular Vesicles Can Deliver Anti-inflammatory and Anti-scarring Activities of Mesenchymal Stromal Cells After Spinal Cord Injury.

Pasquale Romanelli,Dominika Jakubecova,Cornelia Scharler,Mario Gimona,Francisco J Rivera,Pia Zaunmair,Eva Rohde,Dirk Strunk,Lara Bieler,Christina Kreutzer,Sebastien Couillard-Despres,Bruno Benedetti,Karin Pachler,Ludwig Aigner,Heike Mrowetz

doi:10.3389/fneur.2019.01225

Abstract

Spinal cord injury is characterized by initial neural tissue disruption that triggers 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 the 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 2 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 MSC application can be mediated by their secreted EVs. In light of their substantial safety and druggability advantages, EVs may have a high potential in early therapeutic treatment following traumatic spinal cord injury.

Highlights

Traumatic spinal cord injury results from the sudden and largely irreversible disruption of neural parenchyma by mechanical forces, damaging axons and neuronal cell bodies, glia, and blood vessels
We compared the impact of early intravenous delivery of hUCMSCs, with the one of Human umbilical cord (hUC)-mesenchymal stromal cells (MSCs)-extracellular vesicles (EVs), on secondary damages in a rat model of Traumatic spinal cord injury (tSCI)
Rats received a contusion at the thoracic level 8 (Th8), generating a middle to severe spinal cord injury characterized by significant loss of parenchyma at the epicenter of the lesion and the maintenance of a thin rim of white matter

Summary

Introduction

Traumatic spinal cord injury (tSCI) results from the sudden and largely irreversible disruption of neural parenchyma by mechanical forces, damaging axons and neuronal cell bodies, glia, and blood vessels. The latter is results in the formation of edema and ischemia. In contrast to other types of central nervous system (CNS) lesions, the inflammation following tSCI fails to convert into a regenerative type as well as to eventually resolve [5, 7] This harmful inflammation in cases of tSCI underscores the importance of controlling the inflammatory processes as early as possible after initial trauma

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Results

Conclusion