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Regeneration for Spinal Cord Disease: From Pathological Mechanisms to Novel Therapeutic Approaches

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (28 March 2024) | Viewed by 3641

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Special Issue Editor

Dr. Munehisa Shinozaki

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Guest Editor

Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Interests: central nervous system; regeneration; spinal cord injury

Special Issue Information

Dear Colleagues,

The social loss caused by symptoms of spinal cord disease is significant; as a result, various regenerative therapies, such as rehabilitation, cell transplantation, and electrical stimulation, have been implemented as a means to treat it. Still, the effectiveness of regenerative therapies in treating this severe condition is limited. In order to improve these therapies, scientifically adequate evaluations of the pathophysiology, spontaneous recovery, and the post-intervention status of spinal cord injury are required. Furthermore, new insights into the roles of interneurons, mechanisms of plasticity, imaging, and single-cell RNA quantification have the potential to advance regenerative research.

For this Special Issue, we welcome new perspectives on spinal cord regeneration. We intend to provide the most relevant information about available therapeutic strategies administered alone or in combination with others, as well as basic findings on spinal pathological status to enhance these strategies.

Dr. Munehisa Shinozaki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

spinal cord injury
amyotrophic lateral sclerosis
degenerative disease
plasticity
long-term potentiation
muscle synergy
spinal interneuron
cell transplantation
electrical stimulation
rehabilitation

Published Papers (3 papers)

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Research

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14 pages, 2174 KiB

Open AccessArticle

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

by Yoshiharu Takahashi, Takumi Kajitani, Toshiki Endo, Atsushi Nakayashiki, Tomoo Inoue, Kuniyasu Niizuma and Teiji Tominaga

Int. J. Mol. Sci. 2023, 24(19), 14603; https://doi.org/10.3390/ijms241914603 - 27 Sep 2023

Viewed by 879

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. Full article

(This article belongs to the Special Issue Regeneration for Spinal Cord Disease: From Pathological Mechanisms to Novel Therapeutic Approaches)

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18 pages, 7197 KiB

Open AccessArticle

Composite Fibrin/Carbon Microfiber Implants for Bridging Spinal Cord Injury: A Translational Approach in Pigs

by Alexandra Alves-Sampaio, Patricia Del-Cerro and Jorge E. Collazos-Castro

Int. J. Mol. Sci. 2023, 24(13), 11102; https://doi.org/10.3390/ijms241311102 - 5 Jul 2023

Cited by 3 | Viewed by 1151

Abstract

Biomaterials may enhance neural repair after spinal cord injury (SCI) and testing their functionality in large animals is essential to achieve successful clinical translation. This work developed a porcine contusion/compression SCI model to investigate the consequences of myelotomy and implantation of fibrin gel containing biofunctionalized carbon microfibers (MFs). Fourteen pigs were distributed in SCI, SCI/myelotomy, and SCI/myelotomy/implant groups. An automated device was used for SCI. A dorsal myelotomy was performed on the lesion site at 1 day post-injury for removing cloths and devitalized tissue. Bundles of MFs coated with a conducting polymer and cell adhesion molecules were embedded in fibrin gel and used to bridge the spinal cord cavity. Reproducible lesions of about 1 cm in length were obtained. Myelotomy and lesion debridement caused no further neural damage compared to SCI alone but had little positive effect on neural regrowth. The MFs/fibrin gel implant facilitated axonal sprouting, elongation, and alignment within the lesion. However, the implant also increased lesion volume and was ineffective in preventing fibrosis, thus precluding functional neural regeneration. Our results indicate that myelotomy and lesion debridement can be advantageously used for implanting MF-based scaffolds. However, the implants need refinement and pharmaceuticals will be necessary to limit scarring. Full article

(This article belongs to the Special Issue Regeneration for Spinal Cord Disease: From Pathological Mechanisms to Novel Therapeutic Approaches)

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Review

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18 pages, 662 KiB

Open AccessReview

Brain Plasticity in Patients with Spinal Cord Injuries: A Systematic Review

by Andrea Calderone, Davide Cardile, Rosaria De Luca, Angelo Quartarone, Francesco Corallo and Rocco Salvatore Calabrò

Int. J. Mol. Sci. 2024, 25(4), 2224; https://doi.org/10.3390/ijms25042224 - 13 Feb 2024

Cited by 1 | Viewed by 1225

Abstract

A spinal cord injury (SCI) causes changes in brain structure and brain function due to the direct effects of nerve damage, secondary mechanisms, and long-term effects of the injury, such as paralysis and neuropathic pain (NP). Recovery takes place over weeks to months, which is a time frame well beyond the duration of spinal shock and is the phase in which the spinal cord remains unstimulated below the level of injury and is associated with adaptations occurring throughout the nervous system, often referred to as neuronal plasticity. Such changes occur at different anatomical sites and also at different physiological and molecular biological levels. This review aims to investigate brain plasticity in patients with SCIs and its influence on the rehabilitation process. Studies were identified from an online search of the PubMed, Web of Science, and Scopus databases. Studies published between 2013 and 2023 were selected. This review has been registered on OSF under (n) 9QP45. We found that neuroplasticity can affect the sensory-motor network, and different protocols or rehabilitation interventions can activate this process in different ways. Exercise rehabilitation training in humans with SCIs can elicit white matter plasticity in the form of increased myelin water content. This review has demonstrated that SCI patients may experience plastic changes either spontaneously or as a result of specific neurorehabilitation training, which may lead to positive outcomes in functional recovery. Clinical and experimental evidence convincingly displays that plasticity occurs in the adult CNS through a variety of events following traumatic or non-traumatic SCI. Furthermore, efficacy-based, pharmacological, and genetic approaches, alone or in combination, are increasingly effective in promoting plasticity. Full article

(This article belongs to the Special Issue Regeneration for Spinal Cord Disease: From Pathological Mechanisms to Novel Therapeutic Approaches)

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