Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury
Cervical spinal cord trauma represents more than half of the spinal cord injury (SCI) cases worldwide. Respiratory compromise, as well as severe limb motor deficits, are among the main consequences of cervical lesions. In the present work, a Gellan Gum (GG)-based hydrogel modified with GRGDS peptide...
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Frontiers Media S.A.
2020-08-01
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Series: | Frontiers in Bioengineering and Biotechnology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.00984/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eduardo D. Gomes Eduardo D. Gomes Biswarup Ghosh Rui Lima Rui Lima Miguel Goulão Miguel Goulão Miguel Goulão Tiago Moreira-Gomes Tiago Moreira-Gomes Joana Martins-Macedo Joana Martins-Macedo Mark W. Urban Megan C. Wright Jeffrey M. Gimble Nuno Sousa Nuno Sousa Nuno A. Silva Nuno A. Silva Angelo C. Lepore António J. Salgado António J. Salgado |
spellingShingle |
Eduardo D. Gomes Eduardo D. Gomes Biswarup Ghosh Rui Lima Rui Lima Miguel Goulão Miguel Goulão Miguel Goulão Tiago Moreira-Gomes Tiago Moreira-Gomes Joana Martins-Macedo Joana Martins-Macedo Mark W. Urban Megan C. Wright Jeffrey M. Gimble Nuno Sousa Nuno Sousa Nuno A. Silva Nuno A. Silva Angelo C. Lepore António J. Salgado António J. Salgado Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury Frontiers in Bioengineering and Biotechnology cervical spinal cord injury respiratory compromise adipose tissue-derived stem/stromal cells olfactory ensheathing cells modified gellan gum hydrogels |
author_facet |
Eduardo D. Gomes Eduardo D. Gomes Biswarup Ghosh Rui Lima Rui Lima Miguel Goulão Miguel Goulão Miguel Goulão Tiago Moreira-Gomes Tiago Moreira-Gomes Joana Martins-Macedo Joana Martins-Macedo Mark W. Urban Megan C. Wright Jeffrey M. Gimble Nuno Sousa Nuno Sousa Nuno A. Silva Nuno A. Silva Angelo C. Lepore António J. Salgado António J. Salgado |
author_sort |
Eduardo D. Gomes |
title |
Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury |
title_short |
Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury |
title_full |
Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury |
title_fullStr |
Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury |
title_full_unstemmed |
Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord Injury |
title_sort |
combination of a gellan gum-based hydrogel with cell therapy for the treatment of cervical spinal cord injury |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Bioengineering and Biotechnology |
issn |
2296-4185 |
publishDate |
2020-08-01 |
description |
Cervical spinal cord trauma represents more than half of the spinal cord injury (SCI) cases worldwide. Respiratory compromise, as well as severe limb motor deficits, are among the main consequences of cervical lesions. In the present work, a Gellan Gum (GG)-based hydrogel modified with GRGDS peptide, together with adipose tissue-derived stem/stromal cells (ASCs) and olfactory ensheathing cells (OECs), was used as a therapeutic strategy after a C2 hemisection SCI in rats. Hydrogel or cells alone, and a group without treatment, were also tested. Four weeks after injury, compound muscle action potentials (CMAPs) were performed to assess functional phrenic motor neuron (PhMN) innervation of the diaphragm; no differences were observed amongst groups, confirming that the PhMN pool located between C3 and C5 was not affected by the C2 injury or by the treatments. In the same line, the vast majority of diaphragmatic neuromuscular junctions remained intact. Five weeks post-injury, inspiratory bursting of the affected ipsilateral hemidiaphragm was evaluated through EMG recordings of dorsal, medial and ventral subregions of the muscle. All treatments significantly increased EMG amplitude at the ventral portion in comparison to untreated animals, but only the combinatorial group presented increased EMG amplitude at the medial portion of the hemidiaphragm. No differences were observed in forelimb motor function, neither in markers for axonal regrowth (neuronal tracers), astrogliosis (GFAP) and inflammatory cells (CD68). Moreover, using Von Frey testing of mechanical allodynia, it was possible to find a significant effect of the group combining hydrogel and cells on hypersensitivity; rats with a SCI displayed an increased response of the contralateral forelimb to a normally innocuous mechanical stimulus, but after treatment with the combinatorial therapy this behavior was reverted almost to the levels of uninjured controls. These results suggest that our therapeutic approach may have beneficial effects on both diaphragmatic recovery and sensory function. |
topic |
cervical spinal cord injury respiratory compromise adipose tissue-derived stem/stromal cells olfactory ensheathing cells modified gellan gum hydrogels |
url |
https://www.frontiersin.org/article/10.3389/fbioe.2020.00984/full |
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doaj-fa385cee6e824cd9bc277f1f84ddf5d02020-11-25T03:42:27ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-08-01810.3389/fbioe.2020.00984528244Combination of a Gellan Gum-Based Hydrogel With Cell Therapy for the Treatment of Cervical Spinal Cord InjuryEduardo D. Gomes0Eduardo D. Gomes1Biswarup Ghosh2Rui Lima3Rui Lima4Miguel Goulão5Miguel Goulão6Miguel Goulão7Tiago Moreira-Gomes8Tiago Moreira-Gomes9Joana Martins-Macedo10Joana Martins-Macedo11Mark W. Urban12Megan C. Wright13Jeffrey M. Gimble14Nuno Sousa15Nuno Sousa16Nuno A. Silva17Nuno A. Silva18Angelo C. Lepore19António J. Salgado20António J. Salgado21Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalDepartment of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United StatesLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalDepartment of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United StatesLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalDepartment of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Biology, Arcadia University, Glenside, PA, United StatesCenter for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, LA, United StatesLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalDepartment of Neuroscience, Vickie and Jack Farber Institute for Neuroscience, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, United StatesLife and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, PortugalICVS/3B’s – PT Government Associate Laboratory, Guimarães, PortugalCervical spinal cord trauma represents more than half of the spinal cord injury (SCI) cases worldwide. Respiratory compromise, as well as severe limb motor deficits, are among the main consequences of cervical lesions. In the present work, a Gellan Gum (GG)-based hydrogel modified with GRGDS peptide, together with adipose tissue-derived stem/stromal cells (ASCs) and olfactory ensheathing cells (OECs), was used as a therapeutic strategy after a C2 hemisection SCI in rats. Hydrogel or cells alone, and a group without treatment, were also tested. Four weeks after injury, compound muscle action potentials (CMAPs) were performed to assess functional phrenic motor neuron (PhMN) innervation of the diaphragm; no differences were observed amongst groups, confirming that the PhMN pool located between C3 and C5 was not affected by the C2 injury or by the treatments. In the same line, the vast majority of diaphragmatic neuromuscular junctions remained intact. Five weeks post-injury, inspiratory bursting of the affected ipsilateral hemidiaphragm was evaluated through EMG recordings of dorsal, medial and ventral subregions of the muscle. All treatments significantly increased EMG amplitude at the ventral portion in comparison to untreated animals, but only the combinatorial group presented increased EMG amplitude at the medial portion of the hemidiaphragm. No differences were observed in forelimb motor function, neither in markers for axonal regrowth (neuronal tracers), astrogliosis (GFAP) and inflammatory cells (CD68). Moreover, using Von Frey testing of mechanical allodynia, it was possible to find a significant effect of the group combining hydrogel and cells on hypersensitivity; rats with a SCI displayed an increased response of the contralateral forelimb to a normally innocuous mechanical stimulus, but after treatment with the combinatorial therapy this behavior was reverted almost to the levels of uninjured controls. These results suggest that our therapeutic approach may have beneficial effects on both diaphragmatic recovery and sensory function.https://www.frontiersin.org/article/10.3389/fbioe.2020.00984/fullcervical spinal cord injuryrespiratory compromiseadipose tissue-derived stem/stromal cellsolfactory ensheathing cellsmodified gellan gum hydrogels |