Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury

Author:

Takahashi Yoshiharu12,Kajitani Takumi1,Endo Toshiki12ORCID,Nakayashiki Atsushi1,Inoue Tomoo3,Niizuma Kuniyasu145ORCID,Tominaga Teiji1

Affiliation:

1. Department of Neurosurgery, Graduate School of Medicine, Tohoku University, Sendai 980-8572, Japan

2. Department of Neurosurgery, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan

3. Department of Neurosurgery, Saitama Red Cross Hospital, Saitama 330-8553, Japan

4. Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Medicine, Tohoku University, Sendai 980-8576, Japan

5. Department of Neurosurgical Engineering and Translational Neuroscience, Graduate School of Biomedical Engineering, Tohoku University, Sendai 980-8572, Japan

Abstract

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product “CL2020” containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

Funder

MEXT/AMED Translational Research Network Program

JSPS Grant-in-Aid for Scientific Research

HIROMI Medical Research Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. The Phoenix of stem cells: pluripotent cells in adult tissues and peripheral blood;Frontiers in Bioengineering and Biotechnology;2024-07-30

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