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Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection

Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with hum...

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Autores principales: Ganz, Javier, Shor, Erez, Guo, Shaowei, Sheinin, Anton, Arie, Ina, Michaelevski, Izhak, Pitaru, Sandu, Offen, Daniel, Levenberg, Shulamit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671470/
https://www.ncbi.nlm.nih.gov/pubmed/29163001
http://dx.doi.org/10.3389/fnins.2017.00589
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author Ganz, Javier
Shor, Erez
Guo, Shaowei
Sheinin, Anton
Arie, Ina
Michaelevski, Izhak
Pitaru, Sandu
Offen, Daniel
Levenberg, Shulamit
author_facet Ganz, Javier
Shor, Erez
Guo, Shaowei
Sheinin, Anton
Arie, Ina
Michaelevski, Izhak
Pitaru, Sandu
Offen, Daniel
Levenberg, Shulamit
author_sort Ganz, Javier
collection PubMed
description Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with human oral mucosa stem cells (hOMSC) induced to secrete neuroprotective, immunomodulatory, and axonal elongation-associated factors, in a complete spinal cord transection rat model. Rats implanted with induced tissue engineering constructs regained fine motor control, coordination and walking pattern in sharp contrast to the untreated group that remained paralyzed (42 vs. 0%). Immunofluorescence, CLARITY, MRI, and electrophysiological assessments demonstrated a reconnection bridging the injured area, as well as presence of increased number of myelinated axons, neural precursors, and reduced glial scar tissue in recovered animals treated with the induced cell-embedded constructs. Finally, this construct is made of bio-compatible, clinically approved materials and utilizes a safe and easily extractable cell population. The results warrant further research with regards to the effectiveness of this treatment in addressing spinal cord injury.
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spelling pubmed-56714702017-11-21 Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection Ganz, Javier Shor, Erez Guo, Shaowei Sheinin, Anton Arie, Ina Michaelevski, Izhak Pitaru, Sandu Offen, Daniel Levenberg, Shulamit Front Neurosci Neuroscience Spinal cord injury (SCI), involving damaged axons and glial scar tissue, often culminates in irreversible impairments. Achieving substantial recovery following complete spinal cord transection remains an unmet challenge. Here, we report of implantation of an engineered 3D construct embedded with human oral mucosa stem cells (hOMSC) induced to secrete neuroprotective, immunomodulatory, and axonal elongation-associated factors, in a complete spinal cord transection rat model. Rats implanted with induced tissue engineering constructs regained fine motor control, coordination and walking pattern in sharp contrast to the untreated group that remained paralyzed (42 vs. 0%). Immunofluorescence, CLARITY, MRI, and electrophysiological assessments demonstrated a reconnection bridging the injured area, as well as presence of increased number of myelinated axons, neural precursors, and reduced glial scar tissue in recovered animals treated with the induced cell-embedded constructs. Finally, this construct is made of bio-compatible, clinically approved materials and utilizes a safe and easily extractable cell population. The results warrant further research with regards to the effectiveness of this treatment in addressing spinal cord injury. Frontiers Media S.A. 2017-10-31 /pmc/articles/PMC5671470/ /pubmed/29163001 http://dx.doi.org/10.3389/fnins.2017.00589 Text en Copyright © 2017 Ganz, Shor, Guo, Sheinin, Arie, Michaelevski, Pitaru, Offen and Levenberg. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Ganz, Javier
Shor, Erez
Guo, Shaowei
Sheinin, Anton
Arie, Ina
Michaelevski, Izhak
Pitaru, Sandu
Offen, Daniel
Levenberg, Shulamit
Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
title Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
title_full Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
title_fullStr Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
title_full_unstemmed Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
title_short Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
title_sort implantation of 3d constructs embedded with oral mucosa-derived cells induces functional recovery in rats with complete spinal cord transection
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671470/
https://www.ncbi.nlm.nih.gov/pubmed/29163001
http://dx.doi.org/10.3389/fnins.2017.00589
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