Acute intralesional injection of extracellular vesicles secreted by human umbilical cord mesenchymal stromal cells improves BBB score following thoracic contusion in female Fischer rats

DOI:10.34945/F5QK5V

DATASET CITATION

Bieler L., Romanelli P., Jakubec-Hascak D., Benedetti B., Rohde E., Gimona M., Couillard-Despres S. (2025) Acute intralesional injection of extracellular vesicles secreted by human umbilical cord mesenchymal stromal cells improves BBB score following thoracic contusion in female Fischer rats. Open Data Commons for Spinal Cord Injury. ODC-SCI:1285 http://doi.org/10.34945/F5QK5V

ABSTRACT

STUDY PURPOSE: The purpose of this study was to compare the long-term functional outcomes obtained following acute intralesional or intravenous application of EVs secreted by hUC-MSCs in a rat spinal cord contusion model.

DATA COLLECTED: Adult female Fischer-344 rats (n = 40) at 12 weeks of age were used in this project. Thirty rats were subjected to a 200 kdyn contusion at thoracic level 8 followed by acute treatment with extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (huUC-MSCs). In addition, 10 rats only underwent a laminectomy at thoracic level 8 and served as sham controls. Prior to surgery, rats undergoing contusion were randomly divided into three treatment groups, each comprising 10 rats that received the following treatments acutely after contusion: (a) 2 µL of Ringer's-lactate solution (i.pa. vehicle) or (b) 2 µL of Ringer's-lactate solution containing 1.5 × 10^9 extracellular vesicles injected into the parenchyma at the SCI lesion site (i.pa. EVs), or (c) 100 µL of Ringer's-lactate solution containing 1.5 × 10^9 EVs injected intravenously (i.v. EVs) via the tail vein. The number of injected vesicles corresponds to the approximated amount of vesicles secreted by 1 Mio. huUC-MSCs in 24 hours. Four rats were excluded from further analyses due to inadequate contusion, death during surgery or due to post-surgery complications requiring euthanasia (i.pa. vehicle: n = 2; i.pa. EVs: n = 1; i.v. EVs: n = 1). In this dataset, BBB scores and subcores were collected starting from 1 day post-injury until 56 days post-injury.

CONCLUSIONS: On the first day post-tSCI, hindlimbs of rats were nearly paralyzed (BBB score 0.5 ± 0.7). Over the following days, the mobility of joints and the walking pattern progressively recovered in all tSCI groups. Strikingly, from the 2nd week post-injury onward, the recovery of locomotion in i.pa. EVs -treated rats was significantly more robust compared to the recovery following vehicle application. At 56 days post-injury, the BBB score reached 15.2 ± 1.9 in i.pa. EV-treated rats, which corresponds to a consistent forelimb–hindlimb coordination with predominant parallel paw placement at the initial floor contact. In contrast, the BBB scores of vehicle and i.v. EV-treated rats only reached 11.6 ± 0.5 and 12.7 ± 1.7 respectively, which corresponds to consistent weight-supported plantar steps with occasional forelimb–hindlimb coordination. Furthermore, we analyzed the BBB sub-score, which combines various parameters of locomotion, independently of forelimb–hindlimb coordination (maximal score 13). Starting at 28 days post-injury, the BBB sub-score was significantly higher in rats that received i.pa. EV application, as compared to the vehicle-treated rats. Importantly, at 56 days post-injury, the BBB sub-scores of i.pa. and i.v. EV-treated rats (6.1 ± 2.7 and 4.9 ± 1.8, respectively) were significantly higher than the sub-score of vehicle-treated rats (1.6 ± 2.1, p < 0.001), and no significant difference was detected between the EV-treated groups at this time point.

KEYWORDS

Spinal Cord Injury; locomotion; neuroregeneration; motor function; extracellular vesicles; human umbilical cord-derived mesenchymal stromal cells

PROVENANCE / ORIGINATING PUBLICATIONS

• Romanelli Pasquale , Bieler Lara , Heimel Patrick , Škokic Siniša , Jakubecova Dominika , Kreutzer Christina , Zaunmair Pia , Smolcic Tomislav , Benedetti Bruno , Rohde Eva , Gimona Mario , Hercher David , Dobrivojevic Radmilovic Marina , Couillard-Despres Sebastien. doi:10.3389/fncel.2021.795008.

RELEVANT LINKS

NOTES

DATASET INFO

Contact: Couillard-Despres Sebastien (s.couillard-despres@pmu.ac.at)

Lab: Couillard-Despres Lab

ODC-SCI Accession:1285

Records in Dataset: 310

Fields per Record: 27

Last updated: 2025-03-25

Date published: 2025-03-25

Downloads: 6

Files: 2

LICENSE

Creative Commons Attribution License (CC-BY 4.0)

FUNDING AND ACKNOWLEDGEMENTS

Paracelsus Medical University Research Support Fund (PMU-FFF) R-19/01/117-ROM, Austrian Agency for International Cooperation in Education and Research HR02/2018. We gratefully acknowledge financial support through the Project “ExtraNeu” from the State of Salzburg, Austria, and from Land Salzburg/IWB/EFRE 2014-2020 P1812596 “EV-TT” and Land Salzburg/WISS 20125 20102-F1900731-KZP “EV-TT-Bpro”

CONTRIBUTORS

Bieler, Lara [ORCID:0000-0002-1197-0403]

Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria

Romanelli, Pasquale

Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria

Jakubec-Hascak, Dominika [ORCID:0009-0002-9456-0027]

Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria

Benedetti, Bruno [ORCID:0000-0002-4286-5067]

Institute of Experimental Neuroregeneration, Paracelsus Medical University, Austria

Rohde, Eva [ORCID:0000-0001-8692-886X]

GMP Unit, Paracelsus Medical University, Salzburg, Austria; Department of Transfusion Medicine, Salzburger Landeskliniken GesmbH, Paracelsus Medical University, Salzburg, Austria

Gimona, Mario [ORCID:0000-0002-2242-2015]

GMP Unit, Paracelsus Medical University, Salzburg, Austria; Research Program "Nanovesicular Therapies", Paracelsus Medical University, Salzburg, Austria; Ludwig Boltzmann Institute for Nanovesicular Precision Medicine, Salzburg, Austria

Couillard-Despres, Sebastien [ORCID:0000-0002-8486-6412]

Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg, Austria