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Studies of cell-biomaterial interactions and stem cell dynamics using confocal/multi-photon fluorescence microscopy and high content imaging based modeling

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TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Studies of cell-biomaterial interactions and stem cell dynamics using confocal/multi-photon fluorescence microscopy and high content imaging based modeling
Identifier
ETD_3032
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000057611
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Biomedical Engineering
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
Confocal microscopy
Subject (ID = SBJ-3); (authority = ETD-LCSH)
Topic
Stem cells--Research
Subject (ID = SBJ-4); (authority = ETD-LCSH)
Topic
Regenerative medicine
Subject (ID = SBJ-5); (authority = ETD-LCSH)
Topic
Medical microscopy
Abstract (type = abstract)
A strategy in regenerative medicine involves the restitution of functional tissues using biomaterials pre-populated with transplanted cells such as human mesenchymal stem cells (hMSC). However, current design and optimization of extracellular environments to controllably promote tissue-specific regeneration are guided by empiricism, and there is a lack of structure-activity relations underlying cell-biomaterial interactions. This dissertation is focused on using high resolution confocal/multiphoton fluorescence imaging for developing quantifiable descriptors of cell-biomaterial interactions under complex microenvironments, including three-dimensional scaffolds, textural gradients of polymer substrates, and soluble biochemical factors that stimulate differentiation or cancerous transformation. In the first project (Chapter 2), we demonstrated the feasibility of using multiphoton imaging to quantitatively characterize microstructure of 3D biomaterial scaffolds and pseudo-3D cell morphology. This approach was further expanded, in the second project (Chapter 3), to a multidimensional space of cellular and subcellular features (termed cell descriptors) derived from: morphology, reporter protein expression, localization and spatial organization of protein reporters. Using spatially graded polymer blend substrates of both continuous roughness and discrete chemical compositions, we combined high throughput screening with high content analysis to identify both "global" and “high-content” structure-property relationships between cell adhesion and biomaterial properties such as polymer chemistry and topography. In the next project (Chapter 4), we developed a novel molecular screening tool based on the high content descriptors of a nuclear reporter, nuclear mitotic apparatus (NuMA). Using high content imaging, data dimension reduction and machine learning techniques we mapped the nuclear features to different stem cell phenomena, specifically, stem cell lineage commitment to osteogenic versus adipogenic lineages. We reported that NuMA based nuclear descriptors captured the early lineage commitment of hMSC vs self-renewal. Moreover, a combined cytoskeletal and nuclear based “composite” profiling was demonstrated to be a robust tool to parse out not only lineage commitment vs self-renewal but within different lineages (e.g. osteogenic vs adipogenic). In the final project (Chapter 5), nuclear feature based modeling was used to discern early subcellular changes during oncogenic transformation. The utility of this approach was demonstrated by parsing a library of synthetic polymer substrates based on their differential potential to modulate carcinogen-induced transformation of stem cells.
PhysicalDescription
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electronic resource
Extent
xiii, 226 p. : ill.
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application/pdf
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Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Er Liu
Name (ID = NAME-1); (type = personal)
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Liu
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Er
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1979-
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author
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Er Liu
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Moghe
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Prabhas V.
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chair
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Advisory Committee
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Prabhas V. Moghe
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Roth
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Charles M.
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internal member
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Advisory Committee
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Charles M. Roth
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Li
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Cai
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Cai Li
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Androulakis
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Ioannis P.
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Ioannis P. Androulakis
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Doyle
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Doyle Knight
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Kohn
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Joachim
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Joachim Kohn
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Becker
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Matthew L.
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outside member
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Advisory Committee
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Matthew L. Becker
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Rutgers University
Role
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degree grantor
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NamePart
Graduate School - New Brunswick
Role
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school
OriginInfo
DateCreated (qualifier = exact)
2011
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2011-01
Place
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xx
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
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NjNbRU
Identifier (type = doi)
doi:10.7282/T3WS8SXR
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Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Liu
GivenName
Er
Role
Copyright Holder
RightsEvent (ID = RE-1); (AUTHORITY = rulib)
Type
Permission or license
DateTime
2010-12-08 10:23:03
AssociatedEntity (ID = AE-1); (AUTHORITY = rulib)
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Copyright holder
Name
Er Liu
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (ID = AO-1); (AUTHORITY = rulib)
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.
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Technical

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