Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 28 August 2023 / Approved: 29 August 2023 / Online: 30 August 2023 (04:06:09 CEST)

A peer-reviewed article of this Preprint also exists.

Takahashi, Y.; Kajitani, T.; Endo, T.; Nakayashiki, A.; Inoue, T.; Niizuma, K.; Tominaga, T. Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury. Int. J. Mol. Sci. 2023, 24, 14603. Takahashi, Y.; Kajitani, T.; Endo, T.; Nakayashiki, A.; Inoue, T.; Niizuma, K.; Tominaga, T. Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury. Int. J. Mol. Sci. 2023, 24, 14603.

Abstract

Background 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. Methods: 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 12 received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to 3 CL2020-treated animals to selectively ablate human cell functions. Results: 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. Conclusions: Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

Keywords

Muse cell; intravenous administration; rat; spinal cord injury

Subject

Biology and Life Sciences, Neuroscience and Neurology

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