RESEARCH ARTICLE


Intra-Arterial MSC Transplantation Restores Functional Capacity After Skeletal Muscle Trauma



Philipp von Roth*, 1, 2, Georg N Duda2, 3, Piotr Radojewski1, Bernd Preininger1, Kristin Strohschein2, Eric Röhner1, Carsten Perka1, 2, Tobias Winkler1
1 Center for Musculoskeletal Surgery and Julius Wolff Institute, Charité - Universitätsmedizin Berlin, Free and Humboldt-University of Berlin, Germany
2 Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Free and Humboldt-University of Berlin, Germany
3 Berlin-Brandenburg Center for Regenerative Therapies and Julius Wolff Institue, Charité - Universitätsmedizin Berlin, Free and Humboldt-University of Berlin, Germany


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Creative Commons License
© von Roth et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Center for Musculoskeletal Surgery, Charité - Universitätsmedizin Berlin, Free and Humboldt-University of Berlin, Charitéplatz 1, D-10117 Berlin, Germany; Tel: +49 – 30 – 450 659103; Fax: +49 – 30 – 450 522907; E-mail: philipp.roth@charite.de


Abstract

Introduction:

Skeletal muscle trauma leads to severe functional deficits, which cannot be addressed by current treatment options. Our group could show the efficacy of local transplantation of mesenchymal stroma cells (MSCs) for the treatment of injured muscles. While local application of MSCs has proven to be effective, we hypothesized that a selective intra-arterial transplantation would lead to a better distribution of the cells and so improved physiological recovery of muscle function.

Materials and Methodology:

18 female Sprague Dawley rats received an open crush trauma of the left soleus muscle. Autologous MSC were transduced using dsCOP-GFP and 2.5 x 106cells were transplanted into the femoral artery of 9 animals one week after trauma. Control animals (n=9) received a saline injection. Cell tracking, analysis of tissue fibrosis and muscle force measurements were performed after 3 weeks.

Results:

Systemic MSC-therapy improved the muscle force significantly compared to control (fast twitch: 82.4%, tetany: 61.6%, p = 0.02). The histological analysis showed no differences in the quantity of fibrotic tissue. Histological examination revealed no cells in the traumatized muscle tissue 21 days after transplantation.

Conclusions:

The present study demonstrated an effect of systemically administered MSCs in the treatment of skeletal muscle injuries. For possible future therapeutic approaches a systemic application of MSCs seems to present an alternative to a local administration. Such systemic treatment would be preferable since it allows functional improvement and possible cellular concentration at injury sites that are not easily accessible

Keywords:: Muscle, trauma, regeneration, stem cells, stroma cells, intra-arterial, systemic.