Stem Cell Injection in the Hindlimb Skeletal Muscle Enhances Neurorepair in Mice with Spinal Cord Injury

Abstract

Aims: To develop a low-risk, little-invasive stem cell-based method to treat acute spinal cord injuries. methods: Adult mice were submitted to an incomplete spinal cord injury, and mesenchymal stem cells injected intramuscularly into both hindlimbs. Behavior tests and MRI of the spinal cord were periodically performed for up to 6 months, along with immunohistochemical analysis. Immunohistochemical and PCR analysis of the muscles were used to detect the grafted cells as well as the soluble factors released. Results: The stem cell-treated mice presented significant improvements in their motor skills 5 months after treatment. Spinal cord repair was detected by magnetic resonance and immunohistochemistry. In the hindlimb muscles, the stem cells activated muscle and motor neuron repair mechanisms, due to the secretion of several neurotrophic factors. Conclusion: Bone marrow mesenchymal stem cell injection into hindlimb muscles stimulates spinal cord repair in acute spinal cord lesions.

Keywords::

• bone marrow
• intramuscular injection
• in vivo cell tracking
• mesenchymal stem cells
• muscle regeneration
• neurotrophic factors
• spinal cord injury
• spinal cord repair

Financial & competing interests disclosure

This work was supported by the MAPFRE Foundation, FARA (Friedreich’s Ataxia Research Alliance), ASOGAF (Friedreich’s Ataxia association of Granada), Science and Innovation Ministry (MICINN BFU2010–27326), GVA Prometeo grant 2009/028, GVA Prometeo Grant II 2014/014, Tercel (RD06/0010/0023 & RD06/0010/24), MEC-CONSOLIDER CSD2007–00023, Cinco P menos Foundation, EUCOMM, Fundacion Diogenes-Elche city government, and Walk on Project. P Cruz-Martinez is a PhD student of the doctorate program at UAB (Universitat Autònoma Barcelona). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by the MAPFRE Foundation, FARA (Friedreich’s Ataxia Research Alliance), ASOGAF (Friedreich’s Ataxia association of Granada), Science and Innovation Ministry (MICINN BFU2010–27326), GVA Prometeo grant 2009/028, GVA Prometeo Grant II 2014/014, Tercel (RD06/0010/0023 & RD06/0010/24), MEC-CONSOLIDER CSD2007–00023, Cinco P menos Foundation, EUCOMM, Fundacion Diogenes-Elche city government, and Walk on Project. P Cruz-Martinez is a PhD student of the doctorate program at UAB (Universitat Autònoma Barcelona). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript