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Encapsulated Mesenchymal stromal cells for spinal cord injury repair
Descriptive
TitleInfo
Title
Encapsulated Mesenchymal stromal cells for spinal cord injury repair
Name
(type = personal)
NamePart
(type = family)
Barminko
NamePart
(type = given)
Jeffrey Avi
NamePart
(type = date)
1985-
DisplayForm
Jeffrey Barminko
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Shreiber
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(type = given)
David I
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David I Shreiber
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Yarmush
NamePart
(type = given)
Martin l
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Martin l Yarmush
Affiliation
Advisory Committee
Role
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(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Schloss
NamePart
(type = given)
Rene
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Rene Schloss
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Grumet
NamePart
(type = given)
Martin
DisplayForm
Martin Grumet
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
(qualifier = exact)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-10
CopyrightDate
(qualifier = exact)
2012
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Spinal cord injury affects a significant portion of the population and unfortunately, current clinical therapeutic options are limited. The progression of SCI pathology is driven by several cellular and molecular post injury events which culminate in an inhibitory scar. Mesenchymal stromal/stem cells (MSC) robustly produce paracrine factors which successfully attenuate tissue damage and therefore represent a promising cellular SCI therapy. However, current transplantation modalities do not provide control or ensure long term persistence of the cells. To circumvent these limitations, we investigated the efficacy of alginate microencapsulation in developing an implantable vehicle for MSC delivery. We demonstrate that MSCs remain viable after electrostatic encapsulation with alginate and retain paracrine function. Encapsulated MSCs (eMSCs) promote immunomodulatory macrophage action and prevent degradation of hippocampal tissue in an organotypic model of secondary injury. Pre-clinical animal studies demonstrate the feasibility of transplanting eMSC via lumbar puncture (LP). Capsules localize within the intrathecal space for at least 6 weeks after transplantation, without any observable degradation. Free MSC (fMSC) transplants were not detectable 1 week after transplantation, while eMSC persisted for at least 2 weeks after injury. eMSC transplantation led to marked improvements in white matter sparing and locomotor function. Overall, these observations support the inclusion of eMSC for post-SCI therapy. Syringomyelia after SCI can be attributed, in part, to a non-resolving inflammatory presence at the injury site. The Stromal cell represents a key cellular regulator of immune specific functions. Therefore studies were designed to evaluate the regulatory action of MSCs on macrophages during inflammation. MSC secretion of PGE2 promoted macrophage reprogramming by attenuating pro-inflammatory M1 cytokine secretion and enhancing expression of M2 CD206. PGE2 reprogramming was mediated through the EP4 receptor and CREB signaling indirectly, via GSK3-α inhibition. Lastly, MSCs led to a marked increase in CD206 expressing cells at the injury site 1 week after transplantation. The data here support the role of stromal derived PGE2 in facilitating macrophage reprogramming and establishes GSK3-CREB interactions as a possible regulatory checkpoint in macrophage reprogramming. In conclusion, MSC regulation of immune cell plasticity may be responsible, in part, for their efficacy observed post-SCI transplantation.
Subject
(authority = RUETD)
Topic
Biomedical Engineering
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_4344
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xvii, 150 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Jeffrey Avi Barminko
Subject
(authority = ETD-LCSH)
Topic
Spinal cord--Wounds and injuries--Treatment
Subject
(authority = ETD-LCSH)
Topic
Mesenchymal stem cells--Transplantation
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000066610
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
Location
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(authority = marcorg);
(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T39Z93QM
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
Barminko
GivenName
Jeffrey
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2012-10-01 12:38:22
AssociatedEntity
Name
Jeffrey Barminko
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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5377024
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