Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury

Abstract Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulat...

Full description

Bibliographic Details
Main Authors: Henry W. Caplan, Karthik S. Prabhakara, Akshita Kumar, Naama E. Toledano‐Furman, Cecilia Martin, Louis Carrillo, Nicolas F. Moreno, Andrea S. Bordt, Scott D. Olson, Charles S. Cox Jr.
Format: Article
Language:English
Published: Wiley 2020-08-01
Series:Stem Cells Translational Medicine
Subjects:
Online Access:https://doi.org/10.1002/sctm.19-0444
id doaj-3fa4d019f5a44c03b2b2b10829ba1d44
record_format Article
spelling doaj-3fa4d019f5a44c03b2b2b10829ba1d442020-11-25T02:50:09ZengWileyStem Cells Translational Medicine2157-65642157-65802020-08-019890391610.1002/sctm.19-0444Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injuryHenry W. Caplan0Karthik S. Prabhakara1Akshita Kumar2Naama E. Toledano‐Furman3Cecilia Martin4Louis Carrillo5Nicolas F. Moreno6Andrea S. Bordt7Scott D. Olson8Charles S. Cox Jr.9Department of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USADepartment of Pediatric Surgery, McGovern Medical School University of Texas Health Science Center at Houston Houston Texas USAAbstract Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulate microglia activation and polarize them toward a reparative/anti‐inflammatory phenotype have improved outcomes in preclinical models. However, no therapy to date has translated into proven benefits in human patients. Regulatory T cells (Treg) have been shown to downregulate pathologic immune responses of the innate and adaptive immune system across a variety of pathologies. Furthermore, cellular therapy has been shown to augment host Treg responses in preclinical models; yet, studies investigating the use of Treg as a therapeutic for TBI are lacking. In a rodent TBI model, we demonstrate that human umbilical cord blood Treg modulate the central and peripheral immune response after injury in vitro and in vivo.https://doi.org/10.1002/sctm.19-0444cell therapycentral nervous system traumacord bloodmicroglianeuroinflammationregenerative medicine
collection DOAJ
language English
format Article
sources DOAJ
author Henry W. Caplan
Karthik S. Prabhakara
Akshita Kumar
Naama E. Toledano‐Furman
Cecilia Martin
Louis Carrillo
Nicolas F. Moreno
Andrea S. Bordt
Scott D. Olson
Charles S. Cox Jr.
spellingShingle Henry W. Caplan
Karthik S. Prabhakara
Akshita Kumar
Naama E. Toledano‐Furman
Cecilia Martin
Louis Carrillo
Nicolas F. Moreno
Andrea S. Bordt
Scott D. Olson
Charles S. Cox Jr.
Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
Stem Cells Translational Medicine
cell therapy
central nervous system trauma
cord blood
microglia
neuroinflammation
regenerative medicine
author_facet Henry W. Caplan
Karthik S. Prabhakara
Akshita Kumar
Naama E. Toledano‐Furman
Cecilia Martin
Louis Carrillo
Nicolas F. Moreno
Andrea S. Bordt
Scott D. Olson
Charles S. Cox Jr.
author_sort Henry W. Caplan
title Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
title_short Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
title_full Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
title_fullStr Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
title_full_unstemmed Human cord blood‐derived regulatory T‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
title_sort human cord blood‐derived regulatory t‐cell therapy modulates the central and peripheral immune response after traumatic brain injury
publisher Wiley
series Stem Cells Translational Medicine
issn 2157-6564
2157-6580
publishDate 2020-08-01
description Abstract Traumatic brain injury (TBI) causes a profound inflammatory response within the central nervous system and peripheral immune system, which contributes to secondary brain injury and further morbidity and mortality. Preclinical investigations have demonstrated that treatments that downregulate microglia activation and polarize them toward a reparative/anti‐inflammatory phenotype have improved outcomes in preclinical models. However, no therapy to date has translated into proven benefits in human patients. Regulatory T cells (Treg) have been shown to downregulate pathologic immune responses of the innate and adaptive immune system across a variety of pathologies. Furthermore, cellular therapy has been shown to augment host Treg responses in preclinical models; yet, studies investigating the use of Treg as a therapeutic for TBI are lacking. In a rodent TBI model, we demonstrate that human umbilical cord blood Treg modulate the central and peripheral immune response after injury in vitro and in vivo.
topic cell therapy
central nervous system trauma
cord blood
microglia
neuroinflammation
regenerative medicine
url https://doi.org/10.1002/sctm.19-0444
work_keys_str_mv AT henrywcaplan humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT karthiksprabhakara humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT akshitakumar humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT naamaetoledanofurman humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT ceciliamartin humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT louiscarrillo humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT nicolasfmoreno humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT andreasbordt humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT scottdolson humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
AT charlesscoxjr humancordbloodderivedregulatorytcelltherapymodulatesthecentralandperipheralimmuneresponseaftertraumaticbraininjury
_version_ 1724739703209459712