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Alginate-encapsulated mesenchymal stromal cells as a multi-potent therapy for traumatic brain injury

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TitleInfo
Title
Alginate-encapsulated mesenchymal stromal cells as a multi-potent therapy for traumatic brain injury
Name (type = personal)
NamePart (type = family)
Stucky
NamePart (type = given)
Elizabeth Carol
NamePart (type = date)
1977-
DisplayForm
Elizabeth Carol Stucky
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Shreiber
NamePart (type = given)
David I
DisplayForm
David I Shreiber
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Yarmush
NamePart (type = given)
Martin l
DisplayForm
Martin l Yarmush
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
co-chair
Name (type = personal)
NamePart (type = family)
Roth
NamePart (type = given)
Charles
DisplayForm
Charles Roth
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Pedersen
NamePart (type = given)
Henrik
DisplayForm
Henrik Pedersen
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Schloss
NamePart (type = given)
Rene
DisplayForm
Rene Schloss
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (encoding = w3cdtf); (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Primary damage in traumatic brain injury (TBI) occurs instantaneously, and the only method of intervening is prevention. Secondary brain injury, however, involves a complex range of cellular and molecular processes that occur over a period of hours to months after the primary injury, resulting in both immediate cell death and damage, and long-term degenerative changes. Therapies that provide protection against secondary insults and/or restore neural function are critical to survival and functional recovery following TBI. Mesenchymal stromal cells (MSCs) have emerged as a promising therapy, acting as trophic mediators capable of responding to their micro-environment. Current delivery methods, however, limit sustained therapeutic benefit due to lack of long-term persistence, and migration away from the injury site. We have previously developed a method to immobilize MSCs in alginate micro-spheres, enabling greater control and localization. Herein, we evaluated alginate-encapsulated MSC therapy for the ability to target secondary injury components contributing to progressive damage following TBI. We demonstrated that encapsulated MSCs attenuated the neuro-inflammatory response in organotypic hippocampal slice culture (OHSC), more effectively than monolayer MSCs, and identified PGE2 as a key inflammatory mediator produced by MSCs. In contrast to monolayer MSCs, inflammatory signals were not required to stimulate PGE2 production by encapsulated MSCs. Further encapsulation-stimulated changes were revealed in a multiplex panel analyzing 27 MSC-produced cytokines and growth factors. We also determined that our encapsulated MSC treatment primarily targets astrocyte-mediated inflammation, and that constitutively increased levels of PGE2 produced by encapsulated MSCs may be a key contributor to their enhanced inflammatory modulation. Furthermore, encapsulated MSC treatment is capable of up-regulating astrocyte expression of several neurotrophic factors. In addition to modulating inflammation, encapsulated MSCs also prevented ischemia-induced cell death and neurite retraction in OHSC and cerebellar granule neuron cultures, and reduced astrocyte activation markers following in vitro ischemic injury. Overall, we have shown that encapsulated MSCs target multiple components of secondary injury following TBI, including inflammation and ischemia, and provide both anti-inflammatory and neuroprotective benefit. These results suggest that alginate encapsulation of MSCs may not only provide an improved delivery vehicle for transplantation but may also enhance MSC therapeutic benefit for TBI recovery.
Subject (authority = RUETD)
Topic
Chemical and Biochemical Engineering
Subject (authority = ETD-LCSH)
Topic
Brain--Wounds and injuries--Treatment
Subject (authority = ETD-LCSH)
Topic
Mesenchymal stem cells
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6767
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 105 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Elizabeth Carol Stucky
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3DF6T66
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Stucky
GivenName
Elizabeth
MiddleName
Carol
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-09-22 17:55:48
AssociatedEntity
Name
Elizabeth Stucky
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2016-10-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2016.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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