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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Main Authors: Javier Ganz, Erez Shor, Shaowei Guo, Anton Sheinin, Ina Arie, Izhak Michaelevski, Sandu Pitaru, Daniel Offen, Shulamit Levenberg
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-10-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fnins.2017.00589/full
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spelling doaj-592ec32337884285b7a5e5ff53dcd11a2020-11-25T00:42:27ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2017-10-011110.3389/fnins.2017.00589289724Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord TransectionJavier Ganz0Erez Shor1Shaowei Guo2Anton Sheinin3Ina Arie4Izhak Michaelevski5Izhak Michaelevski6Sandu Pitaru7Daniel Offen8Shulamit Levenberg9Department of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Biomedical Engineering, Technion, Haifa, IsraelDepartment of Biomedical Engineering, Technion, Haifa, IsraelDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelDepartment of Oral Biology, School of Dental Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Neurobiology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, IsraelDepartment of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel, IsraelDepartment of Oral Biology, School of Dental Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Human Molecular Genetics and Biochemistry, Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, IsraelDepartment of Biomedical Engineering, Technion, Haifa, IsraelSpinal 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.http://journal.frontiersin.org/article/10.3389/fnins.2017.00589/fullspinal cord injuryoral mucosastem cellstissue engineeringregenerative medicine
collection DOAJ
language English
format Article
sources DOAJ
author Javier Ganz
Erez Shor
Shaowei Guo
Anton Sheinin
Ina Arie
Izhak Michaelevski
Izhak Michaelevski
Sandu Pitaru
Daniel Offen
Shulamit Levenberg
spellingShingle Javier Ganz
Erez Shor
Shaowei Guo
Anton Sheinin
Ina Arie
Izhak Michaelevski
Izhak Michaelevski
Sandu Pitaru
Daniel Offen
Shulamit Levenberg
Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection
Frontiers in Neuroscience
spinal cord injury
oral mucosa
stem cells
tissue engineering
regenerative medicine
author_facet Javier Ganz
Erez Shor
Shaowei Guo
Anton Sheinin
Ina Arie
Izhak Michaelevski
Izhak Michaelevski
Sandu Pitaru
Daniel Offen
Shulamit Levenberg
author_sort Javier Ganz
title 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_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_sort implantation of 3d constructs embedded with oral mucosa-derived cells induces functional recovery in rats with complete spinal cord transection
publisher Frontiers Media S.A.
series Frontiers in Neuroscience
issn 1662-453X
publishDate 2017-10-01
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.
topic spinal cord injury
oral mucosa
stem cells
tissue engineering
regenerative medicine
url http://journal.frontiersin.org/article/10.3389/fnins.2017.00589/full
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