| MR Tracking of Capsules & Cells |
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Wednesday 22 April 2009 |
| Room 316BC |
16:00-18:00 |
Moderators: |
Anna V. Moore and Michal Neeman |
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16:00 |
518. |
Development of a
Magnetosonoporation-Enhanced Stem Cell Labeling
Technique |
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Bensheng Qiu1,
Daohai Xie, Piotr Walczak2, Jesus
Ruiz-Cabello3, Satoshi Minoshima, Jeff
W.M. Bulte2, Xiaoming Yang
1Radiology, University of Washington,
Seattle, WA, USA; 2Johns Hopkins
University; 3Universidad Complutense de
Madrid |
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Monitoring of stem cells
migrating or homing to the targets is essential for
the success of stem cell-based therapies. For
non-invasive magnetic resonance imaging (MRI) to
serially track cell migration, recent efforts have
focused on labeling cells with MR contrast agents,
such as superparamagnetic iron oxide (SPIO)
particles1. The currently-available MR cell labeling
techniques include simple incubation and
magnetoelectroporation. We attempted to develop an
alternative instant cell labeling technique, using
ultrasound to facilitate MR-labeling of cells,
called magneto-sonoporation (MSP), which is based on
the fact that ultrasound can increase cell membrane
permeability to external molecules. |
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16:12 |
519. |
Enhanced Cerebral Targeting of
Magnetically Labeled Glial Precursor Cells Using the
VLA-4/VCAM-1 Adhesion Pathway |
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Piotr Walczak1,2,
Michael Levy2,3, Michael Gorelik2,3,
Douglas A. Kerr2,3, Jeff W.M Bulte1,2
1Radiology, Johns Hopkins University,
Baltimore, MD, USA; 2Institute for Cell
Engineering, Johns Hopkins University, Baltimore,
MD, USA; 3Neurology, Johns Hopkins
University, Baltimore, MD, USA |
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Global cerebral
targeting and homing of therapeutic stem cells is of
key importance for neurodegenerative disorders
having multiple lesions. For cell therapy using
intra-arterial injections, it is critical to achieve
a high level of initial cellular adhesion to
cerebral endothelium before cells can enter the
brain parenchyma. We have exploited the use of the
VLA-4/VCAM-1 endothelial adhesion pathway to enhance
initial endothelial binding by means of transfecting
glial restricted precursors (GRPs) with VLA-4. In an
LPS-induced inflammatory brain model, Feridex-labeled
and VLA-4 over-expressing GRPs showed a dramatically
enhanced global cerebral retention as compared to
those injected in normal brain. |
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16:24 |
520. |
Development of an in Vivo
Functional Assay to Monitor the Effect of SPIO
Labeling on Murine Dendritic Cells Used for Cell
Therapy in MRI |
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Richard Tavaré1,
Gopal Varma1, Pervinder Sagoo2,
Yakup Tanriver2, Tobias Schaeffter1,
Robert Lechler2, Giovanna Lombardi2,
Greg Mullen1
1Division of Imaging Sciences, King's College
London, London, UK; 2Department of
Nephrology and Transplantation, King's College
London, London, UK |
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Dendritic cells are
currently being studied as a therapy for both cancer
and transplant tolerance. Non-invasive imaging of
dendritic cells labeled with superparamagnetic iron
oxides (SPIOs) migrating to lymph nodes allows for
the monitoring of an efficient cellular therapy.
Here, to test the funtion of labeled versus
unlabeled cells, the development of an in vivo
funtional assay is described, as well as serial
imaging of SPIO labeled dendritic cells migrating to
the popliteal lymph node. |
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16:36 |
521. |
Using a 19F MRI Tracer Agent
for in Vivo Tracking of Human Dendritic Cell
Vaccines< |
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Brooke M. Helfer1,
Aaron D. Nelson1, Jelena M. Janjic2,
Eric T. Ahrens2,3, Roberto R. Gil4,
Pawel Kalinski5, Jolanda de Vries6,
Robbie B. Mailliard1
1Research and Development, Celsense, Inc,
Pittsburgh, PA, USA; 2Department of
Biological Sciences, Carnegie Mellon University,
Pittsburgh, PA, USA; 3Pittsburgh NMR
Center for Biomedical Sciences, Carnegie Mellon
University, Pittsburgh, PA, USA; 4Department
of Chemistry, Carnegie Mellon University,
Pittsburgh, PA, USA; 5Department of
Surgery, University of Pittsburgh, Pittsburgh, PA,
USA; 6Department of Pediatric Hemato-Oncology,
Nijmegen Center for Molecular Life Sciences, Radboud
University, Nijmegen, Netherlands |
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Dendritic cells (DCs),
the central antigen presenting cells of the immune
system, have been widely used in clinical trials as
anti-cancer vaccines with mixed success. This is
partially due to inabilities to non-invasively track
adoptively transferred cells after administration.
In this study, we show for the first time that
clinically relevant human DCs can be effectively
labeled in vitro with commercially 19F-tracers
without impact to cell health, phenotype, or
function, allowing these cells to be visualized
post-injection in vivo by 19F-MRI. This study
demonstrates the utility and possible clinical
application of this method for monitoring patients
in cell therapy trials. |
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16:48 |
522. |
Tracking Enhanced Green
Fluorescence Protein (EGFP) and Micrometer-Sized
Particles of Iron Oxide (MPIO) Labeled Mesenchymal
Stem Cells (MSCs) in a Myocardial Infarction Model
with Granulocyte-Colony Stimulating Factor (GCSF)
Modulation |
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Yidong Yang1,2,
Yuhui Yang2, Brianna Klein2,
Nathan Yanasak2, Xingming Shi3,
William Dave Hill4,5, Tom C.-C. Hu1,2
1Medical Physics Program, Georgia Institute of
Technology, Atlanta, GA, USA; 2Department
of Radiology, Medical College of Georgia, Augusta,
GA, USA; 3Department of Pathology,
Medical College of Georgia, Augusta, GA, USA; 4Department
of Cellular Biology and Anatomy, Medical College of
Georgia, Augusta, GA, USA; 5Veterans
Affairs Medical Center, Medical College of Georgia,
Augusta, GA, USA |
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Synopsis: Stem cells
play an important role in tissue repair and
regeneration. In this study, MSCs labeled with EGFP
and MPIO were transplanted into the mouse bone
marrow. It was observed using MRI that the labeled
cells infiltrated and engrafted into the myocardial
injury and adjacent site and lead to gradual signal
attenuation. Furthermore, the GCSF potentially
modulated the infiltration rate of labeled MSCs and
enhanced the signal attenuation. Results from this
study suggest a useful method for the development of
drugs designed to modulate the stem cell
mobilization process. |
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17:00 |
523. |
Ferritin Overexpression for
Molecular Imaging of Transplanted Cells |
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Anna Naumova1,
Hans Reinecke2,3, Vasily Yarnykh1,
Chun Yuan1, Charles Murry2,3
1Radiology, University of Washington, Seattle,
WA, USA; 2Pathology, University of
Washington, Seattle, WA, USA; 3Center for
Cardiovascular Biology, Seattle, WA, USA |
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We are developing
genetically-based technique for molecular imaging of
the MRI gene reporter ferritin to enable noninvasive
assessment of cell survival and biodistribution
after transplantation into infarcted rodent heart.
pcDNA3-HAFerr transduction vector encoding ferritin
was successfully constructed. Mouse skeletal
myoblasts transduced by the vector increased
intracellular iron stores, confirmed by Prussian
blue staining and yielding a robust detectable
effect on T2 and T1 relaxation times in vitro.
Ferritin overexpression did not affect cell
viability, proliferation and differentiation into
multinucleated myotubes. Our pilot studies are
encouraging for further in vivo studies of
transplanted cells in a beating heart. |
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17:12 |
524. |
MR-Visible and
Immunoprotective Alginate Microcapsules for
Treatment of Fulminant Liver Failure |
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Thomas W. Link1,2,
Dian Arifin2,3, Chris M. Long1,2,
Piotr Walczak2,3, Naser Muja2,3,
Jeff W.M Bulte2,3
1Biomedical Engineering, Johns Hopkins
University, Baltimore, MD, USA; 2Department
of Radiology, Johns Hopkins University School of
Medicine, Baltimore, MD, USA; 3Cellular
Imaging Section, Institute for Cell Engineering,
Johns Hopkins University School of Medicine,
Baltimore, MD, USA |
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20-30% of patients with
fulminant liver failure die waiting for a transplant
due to shortage of donors. Microencapsulated human
hepatocytes have the potential to provide a bridge
to transplantation. Feridex was incorporated into
novel protamine sulfate cross-linked alginate
microcapsules to create MR-visible magnetocapsules.
Magneto-encapsulated bioluminescent human
hepatocytes were characterized in vitro, and
injected into the peritoneal cavity of normal mice.
Bioluminescent imaging and detection of human
albumin by ELISA demonstrated that hepatocytes
remained viable and functional for at least 2 weeks.
Magnetocapsules were clearly visible as
hypointensities throughout the peritoneal cavity. |
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17:24 |
525. |
Facilitated Detection and
Quantification of Theragnostic Magnetocapsules by
Analyzing MRI Susceptibility Perturbations |
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Parker H. Mills1,2, Thomas Link3,
Aravind Arepally3, Joseph D. Thompson4,
Jeff W.M. Bulte3, Eric T. Ahrens1,2
1Department of Biological Sciences, Carnegie
Mellon University, Pittsburgh, PA, USA; 2Pittsburgh
NMR Center for Biomedical Research, Pittsburgh, PA,
USA; 3Institute for Cell Engineering,
Johns Hopkins School of Medicine, Baltimore, MD,
USA; 4Division of Materials Science &
Technology, Group 10, Los Alamos National
Laboratory, Los Alamos, NM, USA |
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Non-invasive studies
have monitored the delivery and engraftment of
pancreatic islets encapsulated in alginate shells
containing Feridex, an FDA-approved
superparamagnetic iron-oxide (SPIO). These
magnetocapsules are permeable to metabolites, but
not native antibodies, thus reducing or avoiding
immunosuppressive therapy. Here we apply a newly
developed post-processing method, Phase map
cross-correlation Detection and Quantification (PDQ),
to gel phantoms containing ~103, 450 μm diameter
magnetocapsules. PDQ automatically identified and
counted magnetocapsules, accurately measuring their
magnetic moment (within 1-21% of SQUID-measured
values). PDQ can potentially search tissue volumes
for absolute magnetocapsule numbers, providing
insight on overall islet immunoprotection and
survival. PDQ requires no special pulse sequences
and works on previously-acquired data. |
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17:36 |
526. |
Novel Trimodal Gadolinium-Gold
Microcapsules for Simultaneous Immunoprotection and
Positive Contrast MRI, X-Ray, and Ultrasound Imaging
of Human Pancreatic Islet Cells |
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Dian Respati Arifin1,2,
Christopher Long1,2, Assaf A. Gilad1,2,
Sameer Manek2,3, Emma Call2,
Christophe Alric4, Stephane Roux4,
Olivier Tillement4, Thomas W. Link2,3,
Aravind Arepally1, Jeff W.M. Bulte1,2
1Radiology and Radiological Sciences, Johns
Hopkins University School of Medicine, Baltimore,
MD, USA; 2Cellular Imaging Section,
Institute for Cell Engineering, Johns Hopkins
University School of Medicine; 3Biomedical
Engineering, Johns Hopkins University School of
Medicine; 4Laboratoire de Physico-Chimie
des Materiaux Luminescents, Universite Claude
Bernard Lyon 1, Lyon, France |
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Transplantation of
pancreatic islet cells is a potential treatment for
type I diabetes. Pancreatic islet cells and novel
gold nanoparticles functionalized with
DTDTPA:gadolinium chelates (GadoGold) were
encapsulated inside immunoprotective microcapsules.
The viability and functionality of cells
encapsulated in GadoGold microcapsules was
demonstrated in vitro and in vivo in diabetic
mice. The capsules were readily imaged with 9.4
Tesla MRI, micro-CT, and a 40 MHz ultrasound imager.
GadoGold microcapsules have potential for cell
engraftment providing a means to monitor
transplanted cells in vivo using MRI , X-ray
and/or ultrasound imaging. |
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17:48 |
527. |
Multifunctional Perfluorinated
Microcapsules for Mesenchymal Stem Cell Delivery and
Engraftment Tracking Using 19F MRI,
X-Ray, and Ultrasound |
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Yingli Fu1,
Dorota A. Kedziorek1, Ronald Ouwerkerk1,
Steven M. Shea2, Nicole Azene1,
Aravind Arepally1, Jeff WM Bulte1,3,
Robert Krieg4, Frank Wacker1,
Dara L. Kraitchman1
1Russell H. Morgan Department of Radiology and
Radiological Science, Johns Hopkins University,
Baltimore, MD, USA; 2Imaging and
Visualization, Siemens Research Corporate, Inc.,
Baltimore, MD, USA; 3Institute of Cell
Engineering, Johns Hopkins University, Baltimore,
MD, USA; 4Siemens AG Healthcare Sector,
Erlangen, Germany |
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Mesenchymal stem cell (MSC)
transplantation is a promising angiogenesis
induction therapy for peripheral arterial disease.
To immunoprotect MSC after transplantation and
monitor MSC delivery and track engraftment
noninvasively in vivo, we have developed
novel multifunctional perfluoroctylbromide
microcapsules (PFOB Caps). Our strategy couples
microencapsulation techniques with multi-modality
imaging, and converts direct cell labeling and
tracking task into microcapsule labeling and
tracking task. In vitro, MSC viability within
PFOB Caps was enhanced as compared to that in
unlabeled capsules. The visibility of PFOB Caps was
demonstrated in vitro and in vivo
using clinical X-ray, c-arm CT, ultrasound, and
19F MR imaging systems. |
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