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

• Published in: Journal of neurosurgery. Spine Vol. 34; no. 4; p. 648
• Main Authors: Kajitani, Takumi, Endo, Toshiki, Iwabuchi, Naoya, Inoue, Tomoo, Takahashi, Yoshiharu, Abe, Takatsugu, Niizuma, Kuniyasu, Tominaga, Teiji
• Format: Journal Article
• Language: English
• Published: United States 01.04.2021
• Subjects: Administration, Intravenous - methods; Alprostadil - therapeutic use; Animals; Cell Differentiation - physiology; Disease Models, Animal; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - physiology; Neurons - cytology; Rats; Rats, Sprague-Dawley; Spinal Cord - cytology; Spinal Cord Injuries - therapy; spinal cord injury; cell transplantation; intravenous administration; rat; Muse cell
• ISSN: 1547-5646
• DOI: 10.3171/2020.7.SPINE20293

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). 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. 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. 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.