TY  - JOUR
A1  - Ashmwe, Mohamed
A1  - Posa, Katja
A1  - Rührnößl, Alexander
A1  - Heinzel, Johannes Christoph
A1  - Heimel, Patrick
A1  - Mock, Michael
A1  - Schädl, Barbara
A1  - Keibl, Claudia
A1  - Couillard-Despres, Sebastien
A1  - Redl, Heinz
A1  - Mittermayr, Rainer
A1  - Hercher, David
T1  - Effects of Extracorporeal Shockwave Therapy on Functional Recovery and Circulating miR-375 and miR-382-5p after Subacute and Chronic Spinal Cord Contusion Injury in Rats
JF  - Biomedicines
N2  - Extracorporeal shockwave therapy (ESWT) can stimulate processes to promote regeneration, including cell proliferation and modulation of inflammation. Specific miRNA expression panels have been established to define correlations with regulatory targets within these pathways. This study aims to investigate the influence of low-energy ESWT-applied within the subacute and chronic phase of SCI (spinal cord injury) on recovery in a rat spinal cord contusion model. Outcomes were evaluated by gait analysis, µCT and histological analysis of spinal cords. A panel of serum-derived miRNAs after SCI and after ESWT was investigated to identify injury-, regeneration- and treatment-associated expression patterns. Rats receiving ESWT showed significant improvement in motor function in both a subacute and a chronic experimental setting. This effect was not reflected in changes in morphology, µCT-parameters or histological markers after ESWT. Expression analysis of various miRNAs, however, revealed changes after SCI and ESWT, with increased miR-375, indicating a neuroprotective effect, and decreased miR-382-5p potentially improving neuroplasticity via its regulatory involvement with BDNF. We were able to demonstrate a functional improvement of ESWT-treated animals after SCI in a subacute and chronic setting. Furthermore, the identification of miR-375 and miR-382-5p could potentially provide new targets for therapeutic intervention in future studies.
KW  - Tissue Engineering
KW  - ESWT
KW  - Spinal Cord Injury
Y1  - 
U6  - http://dx.doi.org/https://doi.org/10.3390/biomedicines10071630
VL  - 2022
IS  - 10(7)
SP  - 1630
ER  - 
TY  - JOUR
A1  - Romanelli, Pasquale
A1  - Bieler, Lara
A1  - Heimel, Patrick
A1  - Škokić, Siniša
A1  - Jakubecova, Dominika
A1  - Kreutzer, Christina
A1  - Zaunmair, Pia
A1  - Smolčić, Tomislav
A1  - Benedetti, Bruno
A1  - Rohde, Eva
A1  - Gimona, Mario
A1  - Hercher, David
A1  - Dobrivojević Radmilović, Marina
A1  - Couillard-Despres, Sebastien
T1  - Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
JF  - Front Cell Neurosci
N2  - Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.
KW  - exosomes
KW  - inflammation
KW  - locomotion
KW  - neuroimaging
KW  - motor function
Y1  - 
U6  - http://dx.doi.org/10.3389/fncel.2021.795008
VL  - 15
ER  -