An Assessment of Gadonanotubes as Magnetic Nanolabels for Improved Stem Cell Detection and Retention in Cardiomyoplasty

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dc.contributor.advisorWilson, Lon J.en_US
dc.contributor.committeeMemberMatsuda, Seiichi P. T.en_US
dc.contributor.committeeMemberJacot, Jeffrey G.en_US
dc.contributor.committeeMemberPerin, Emerson C.en_US
dc.contributor.committeeMemberCabreira, Maria da Graçaen_US
dc.creatorTran, Lesaen_US
dc.date.accessioned2013-07-24T19:49:36Zen_US
dc.date.accessioned2013-07-24T19:49:43Zen_US
dc.date.available2013-07-24T19:49:36Zen_US
dc.date.available2013-07-24T19:49:43Zen_US
dc.date.created2012-12en_US
dc.date.issued2013-07-24en_US
dc.date.submittedDecember 2012en_US
dc.date.updated2013-07-24T19:49:43Zen_US
dc.description.abstractIn this work, gadolinium-based carbon nanocapsules are developed as a novel nanotechnology that addresses the shortcomings of current diagnostic and therapeutic methods of stem cell-based cardiomyoplasty. With cardiovascular disease (CVD) responsible for approximately 30% of deaths worldwide, the growing need for improved cardiomyoplasty has spurred efforts in nanomedicine to develop innovative techniques to enhance the therapeutic retention and diagnostic tracking of transplanted cells. Having previously been demonstrated as a high-performance T1-weighted magnetic resonance imaging (MRI) contrast agent, Gadonanotubes (GNTs) are shown for the first time to intracellularly label pig bone marrow-derived mesenchymal stem cells (MSCs). Without the use of a transfection agent, micromolar concentrations of GNTs deliver up to 10^9 Gd(III) ions per cell, allowing for MSCs to be visualized in a 1.5 T clinical MRI scanner. The cellular response to the intracellular incorporation of GNTs is also assessed, revealing that GNTs do not compromise the viability, differentiation potential, or phenotype characteristics of the MSCs. However, it is also found that GNT-labeled MSCs exhibit a decreased response to select cell adhesion proteins and experience a non-apoptotic, non-proliferative cell cycle arrest, from which the cells recover 48 h after GNT internalization. In tandem with developing GNTs as a new stem cell diagnostic agent, this current work also explores for the first time the therapeutic application of the magnetically-active GNTs as a magnetic facilitator to increase the retention of transplanted stem cells during cardiomyoplasty. In vitro flow chamber assays, ex vivo perfusion experiments, and in vivo porcine injection procedures all demonstrate the increased magnetic-assisted retention of GNT-labeled MSCs in the presence of an external magnetic field. These studies prove that GNTs are a powerful ‘theranostic’ agent that provides a novel platform to simultaneously monitor and improve the therapeutic nature of stem cells for the treatment of CVD. It is expected that this new nanotechnology will further catalyze the development of cellular cardiomyoplasty and other stem cell-based therapies for the prevention, detection, and treatment of human diseases.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationTran, Lesa. "An Assessment of Gadonanotubes as Magnetic Nanolabels for Improved Stem Cell Detection and Retention in Cardiomyoplasty." (2013) Diss., Rice University. <a href="https://hdl.handle.net/1911/71698">https://hdl.handle.net/1911/71698</a>.en_US
dc.identifier.slug123456789/ETD-2012-12-235en_US
dc.identifier.urihttps://hdl.handle.net/1911/71698en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectMesenchymal stem cellsen_US
dc.subjectMagnetic resonance imaging (MRI)en_US
dc.subjectNanoparticlesen_US
dc.subjectCell labelingen_US
dc.subjectSingle-walled carbon nanotubesen_US
dc.subjectGadonanotube (GNT)en_US
dc.subjectCellular cardiomyoplastyen_US
dc.titleAn Assessment of Gadonanotubes as Magnetic Nanolabels for Improved Stem Cell Detection and Retention in Cardiomyoplastyen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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