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Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model

Traumatic brain injury (TBI) causes both physical disruption of the blood brain barrier (BBB) and altered immune responses that can lead to significant secondary brain injury and chronic inflammation within the central nervous system (CNS). Cell therapies, including mesenchymal stromal cells (MSC),...

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Autores principales: Caplan, Henry W., Prabhakara, Karthik S., Toledano Furman, Naama E., Zorofchian, Soheil, Martin, Cecilia, Xue, Hasen, Olson, Scott D., Cox, Charles S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153465/
https://www.ncbi.nlm.nih.gov/pubmed/34038436
http://dx.doi.org/10.1371/journal.pone.0251601
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author Caplan, Henry W.
Prabhakara, Karthik S.
Toledano Furman, Naama E.
Zorofchian, Soheil
Martin, Cecilia
Xue, Hasen
Olson, Scott D.
Cox, Charles S.
author_facet Caplan, Henry W.
Prabhakara, Karthik S.
Toledano Furman, Naama E.
Zorofchian, Soheil
Martin, Cecilia
Xue, Hasen
Olson, Scott D.
Cox, Charles S.
author_sort Caplan, Henry W.
collection PubMed
description Traumatic brain injury (TBI) causes both physical disruption of the blood brain barrier (BBB) and altered immune responses that can lead to significant secondary brain injury and chronic inflammation within the central nervous system (CNS). Cell therapies, including mesenchymal stromal cells (MSC), have been shown to restore BBB integrity and augment endogenous splenic regulatory T cells (Treg), a subset of CD4+ T cells that function to regulate immune responses and prevent autoimmunity. We have recently shown that infusion of human cord blood-derived Treg decreased neuroinflammation after TBI in vivo and in vitro. However, while both cells have demonstrated anti-inflammatory and regenerative potential, they likely utilize differing, although potentially overlapping, mechanisms. Furthermore, studies investigating these two cell types together, as a combination therapy, are lacking. In this study, we compared the ability of Treg+MSC combination therapy, as well as MSC and Treg monotherapies, to improve BBB permeability in vivo and suppress inflammation in vitro. While Treg+MSC combination did not significantly augment potency in vivo, our in vitro data demonstrates that combination therapy may augment therapeutic potency and immunosuppressive potential compared to Treg or MSC monotherapy.
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spelling pubmed-81534652021-06-09 Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model Caplan, Henry W. Prabhakara, Karthik S. Toledano Furman, Naama E. Zorofchian, Soheil Martin, Cecilia Xue, Hasen Olson, Scott D. Cox, Charles S. PLoS One Research Article Traumatic brain injury (TBI) causes both physical disruption of the blood brain barrier (BBB) and altered immune responses that can lead to significant secondary brain injury and chronic inflammation within the central nervous system (CNS). Cell therapies, including mesenchymal stromal cells (MSC), have been shown to restore BBB integrity and augment endogenous splenic regulatory T cells (Treg), a subset of CD4+ T cells that function to regulate immune responses and prevent autoimmunity. We have recently shown that infusion of human cord blood-derived Treg decreased neuroinflammation after TBI in vivo and in vitro. However, while both cells have demonstrated anti-inflammatory and regenerative potential, they likely utilize differing, although potentially overlapping, mechanisms. Furthermore, studies investigating these two cell types together, as a combination therapy, are lacking. In this study, we compared the ability of Treg+MSC combination therapy, as well as MSC and Treg monotherapies, to improve BBB permeability in vivo and suppress inflammation in vitro. While Treg+MSC combination did not significantly augment potency in vivo, our in vitro data demonstrates that combination therapy may augment therapeutic potency and immunosuppressive potential compared to Treg or MSC monotherapy. Public Library of Science 2021-05-26 /pmc/articles/PMC8153465/ /pubmed/34038436 http://dx.doi.org/10.1371/journal.pone.0251601 Text en © 2021 Caplan et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Caplan, Henry W.
Prabhakara, Karthik S.
Toledano Furman, Naama E.
Zorofchian, Soheil
Martin, Cecilia
Xue, Hasen
Olson, Scott D.
Cox, Charles S.
Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
title Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
title_full Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
title_fullStr Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
title_full_unstemmed Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
title_short Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
title_sort human-derived treg and msc combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153465/
https://www.ncbi.nlm.nih.gov/pubmed/34038436
http://dx.doi.org/10.1371/journal.pone.0251601
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