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Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury

Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericy...

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Autores principales: Vawda, Reaz, Badner, Anna, Hong, James, Mikhail, Mirriam, Lakhani, Alam, Dragas, Rachel, Xhima, Kristiana, Barretto, Tanya, Librach, Clifford L., Fehlings, Michael G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591557/
https://www.ncbi.nlm.nih.gov/pubmed/30912623
http://dx.doi.org/10.1002/sctm.18-0192
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author Vawda, Reaz
Badner, Anna
Hong, James
Mikhail, Mirriam
Lakhani, Alam
Dragas, Rachel
Xhima, Kristiana
Barretto, Tanya
Librach, Clifford L.
Fehlings, Michael G.
author_facet Vawda, Reaz
Badner, Anna
Hong, James
Mikhail, Mirriam
Lakhani, Alam
Dragas, Rachel
Xhima, Kristiana
Barretto, Tanya
Librach, Clifford L.
Fehlings, Michael G.
author_sort Vawda, Reaz
collection PubMed
description Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericytic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vascular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compression/contusion injury was induced at C7‐T1 in adult female rats, followed by an intravenous tail vein infusion 1 hour post‐SCI of (a) term‐birth human umbilical cord perivascular cells (HUCPVCs); (b) first‐trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrificed at 24 hours or 10 weeks post‐SCI and immunohistochemistry and ultrasound imaging were performed. Both term and FTM HUCPVC‐infused rats displayed improved (p < .05) grip strength compared with vehicle controls. However, only FTM HUCPVC‐infusion led to significant weight gain. All cell infusion treatments resulted in reduced glial scarring (p < .05). Cell infusion also led to increased axonal, myelin, and vascular densities (p < .05). Although post‐traumatic cavity volume was reduced with cell infusion, this did not reach significance. Taken together, we demonstrate selective long‐term functional recovery alongside histological improvements with HUCPVC infusion in a clinically relevant model of cervical SCI. Our findings highlight the potential of these cells for acute therapeutic intervention after SCI.
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spelling pubmed-65915572019-07-09 Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury Vawda, Reaz Badner, Anna Hong, James Mikhail, Mirriam Lakhani, Alam Dragas, Rachel Xhima, Kristiana Barretto, Tanya Librach, Clifford L. Fehlings, Michael G. Stem Cells Transl Med Fetal and Neonatal Stem Cells Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericytic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vascular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compression/contusion injury was induced at C7‐T1 in adult female rats, followed by an intravenous tail vein infusion 1 hour post‐SCI of (a) term‐birth human umbilical cord perivascular cells (HUCPVCs); (b) first‐trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrificed at 24 hours or 10 weeks post‐SCI and immunohistochemistry and ultrasound imaging were performed. Both term and FTM HUCPVC‐infused rats displayed improved (p < .05) grip strength compared with vehicle controls. However, only FTM HUCPVC‐infusion led to significant weight gain. All cell infusion treatments resulted in reduced glial scarring (p < .05). Cell infusion also led to increased axonal, myelin, and vascular densities (p < .05). Although post‐traumatic cavity volume was reduced with cell infusion, this did not reach significance. Taken together, we demonstrate selective long‐term functional recovery alongside histological improvements with HUCPVC infusion in a clinically relevant model of cervical SCI. Our findings highlight the potential of these cells for acute therapeutic intervention after SCI. John Wiley & Sons, Inc. 2019-03-26 /pmc/articles/PMC6591557/ /pubmed/30912623 http://dx.doi.org/10.1002/sctm.18-0192 Text en © 2019 The Authors. stem cells translational medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Fetal and Neonatal Stem Cells
Vawda, Reaz
Badner, Anna
Hong, James
Mikhail, Mirriam
Lakhani, Alam
Dragas, Rachel
Xhima, Kristiana
Barretto, Tanya
Librach, Clifford L.
Fehlings, Michael G.
Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury
title Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury
title_full Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury
title_fullStr Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury
title_full_unstemmed Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury
title_short Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury
title_sort early intravenous infusion of mesenchymal stromal cells exerts a tissue source age‐dependent beneficial effect on neurovascular integrity and neurobehavioral recovery after traumatic cervical spinal cord injury
topic Fetal and Neonatal Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591557/
https://www.ncbi.nlm.nih.gov/pubmed/30912623
http://dx.doi.org/10.1002/sctm.18-0192
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