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Approaches to improving the therapeutic potential of Mesenchymal Stromal Cells

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TitleInfo
Title
Approaches to improving the therapeutic potential of Mesenchymal Stromal Cells
Name (type = personal)
NamePart (type = family)
Gray
NamePart (type = given)
Andrea
NamePart (type = date)
1987-
DisplayForm
Andrea Gray
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Yarmush
NamePart (type = given)
Martin
DisplayForm
Martin Yarmush
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Schloss
NamePart (type = given)
Rene
DisplayForm
Rene Schloss
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Maguire
NamePart (type = given)
Timothy
DisplayForm
Timothy Maguire
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Banerjee
NamePart (type = given)
Debabrata
DisplayForm
Debabrata Banerjee
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)
Mesenchymal stromal cells (MSCs) hold great potential as a cellular therapy due in part to their tissue protective and regenerative abilities, achieved via the secretion of many bioactive molecules and induced by microenvironmental cues including soluble factors. However, translation of MSCs into the clinic, where variability exists amongst both MSC donors and recipients, has not resulted in dramatic success. Efforts to identify activation inputs that promote specific MSC phenotypes have been inconsistent and lack systematic optimization. The goal of our work is to address these hurdles using a combination of approaches. We aimed to (1) develop a systematic approach for optimizing activation parameters (type and/or combinations of activating molecule, concentration, and duration of exposure) that enhance MSC immunomodulation, (2) characterize MSCs treated with the resulting pre-activation protocol, and (3) test the performance of the pre-activation protocol using multiple MSC donors. In a high throughput in vitro screening assay designed using fractional factorial design of experiments, we identified interleukin (IL)-1β and lipopolysaccharide (LPS), individually and in combination, as optimal activators of MSC attenuation of pro-inflammatory macrophage tumor necrosis factor (TNF)-α production via prostaglandin E2 (PGE2) secretion. Further optimization of dose and duration of pre-activation, however, revealed that brief (1 hour) exposure of to 1 ng/mL IL-1β alone resulted in the highest sustained upregulation of PGE2 secretion post-activation. This pre-activation protocol generated MSCs whose PGE2 secretion was more sensitive to induction by secondary inflammatory molecules than MSCs with no pre-activation. IL-1β pre-activation led to enhanced MSC-mediated attenuation of macrophage TNF-α in a co-culture assay. This protocol was also successful in enhancing these functions for multiple MSC donors, although variability was noted in the absolute secretion levels of PGE2, the level of improvement in macrophage modulation, and the correlation of MSC PGE2 and macrophage TNF-α. Using the previous assays, we found that alginate encapsulated MSCs retained the ability to respond to activation factors. Statistical analysis revealed that macrophage TNF-α level was more significantly a function of PGE2 level, MSC activation factor, and macrophage donor rather than MSC culture format (monolayer versus encapsulated).
Subject (authority = RUETD)
Topic
Biomedical Engineering
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6762
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xvii, 168 p. : ill.)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Immune response--Regulation
Subject (authority = ETD-LCSH)
Topic
Cellular therapy
Note (type = statement of responsibility)
by Andrea Gray
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/T3154K14
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Gray
GivenName
Andrea
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-09-22 11:11:51
AssociatedEntity
Name
Andrea Gray
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)
2017-10-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2017.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ETD
OperatingSystem (VERSION = 5.1)
windows xp
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