Association of intravenous administration of human Muse cells with deficit amelioration in a rat model of spinal cord injury

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  • 1 Department of Neurosurgery, Tohoku University Graduate School of Medicine;
  • 2 Department of Neurosurgery, Sendai Medical Center;
  • 3 Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Biomedical Engineering; and
  • 4 Department of Neurosurgical Engineering and Translational Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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OBJECTIVE

Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells, which can be harvested from the bone marrow. After transplantation, Muse cells can migrate to an injured site of the body and exert repair effects. However, it remains unknown whether Muse cell transplantation can be an effective treatment in spinal cord injury (SCI).

METHODS

The authors used a rat model of thoracic spinal cord contusion injury. For Muse cell transplantation, the clinical product CL2020 containing 300,000 Muse cells was administered intravenously 1 day after midthoracic SCI. Animals were divided into CL2020 (n = 11) and vehicle-treated (n = 15) groups. Behavioral and histological evaluations were conducted over a period of 8 weeks to see whether intravenous CL2020 administration provided therapeutic effects for SCI. The effects of human-selective diphtheria toxin on reversion of the therapeutic effects of CL2020 were also investigated.

RESULTS

Hindlimb motor function significantly improved after CL2020 transplantations. Importantly, the effects were reverted by the human-selective diphtheria toxin. In immunohistochemical analyses, the cystic cavity formed after the injury was smaller in the CL2020 group. Furthermore, higher numbers of descending 5-hydroxytryptamine (5-HT) fibers were preserved distal to the injury site after CL2020 administration. Eight weeks after the injury, Muse cells in CL2020 were confirmed to differentiate most predominantly into neuronal cells in the injured spinal cord.

CONCLUSIONS

Following SCI, Muse cells in CL2020 can reach the injured spinal cord after intravenous administration and differentiate into neuronal cells. Muse cells in CL2020 facilitated nerve fiber preservation and exerted therapeutic potential for severe SCI.

ABBREVIATIONS BBB = Basso, Beattie, Bresnahan; GFAP = glial fibrillary acidic protein; GST-pi = glutathione S-transferase pi; hMit = human mitochondria; IH = Infinite Horizon; MAP-2 = microtubule-associated protein-2; MSC = mesenchymal stem cell; Muse = multilineage-differentiating stress-enduring; SCI = spinal cord injury; SSEA-3 = stage-specific embryonic antigen 3; 5-HT = 5-hydroxytryptamine.

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Contributor Notes

Correspondence Toshiki Endo: Tohoku University Graduate School of Medicine, Sendai, Japan. endo@nsg.med.tohoku.ac.jp.

INCLUDE WHEN CITING Published online January 1, 2021; DOI: 10.3171/2020.7.SPINE20293.

Disclosures This study was partially supported by the MEXT/AMED Translational Research Network Program (J190000613), a JSPS Grant-in-Aid for Scientific Research (C), the HIROMI Medical Research Foundation, the Ichiro Kanehara Foundation, the SENSHIN Medical Research Foundation, the Okinaka Memorial Institute for Medical Research, and co-research expenses with Life Science Institute Inc. (LSII; Tokyo, Japan). Dr. Takatsugu Abe, Prof. Kuniyasu Niizuma, and Prof. Teiji Tominaga are parties to a joint research agreement with LSII. Prof. Niizuma has a contract of a clinical trial agreement with LSII. Prof. Tominaga received consulting fees from LSII.

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