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cell sorting [FACS]), and in vivo imaging using firefly luciferase ( luc ) for
high-throughput bioluminescence imaging or the herpes simplex virus type
1-truncated thymidine kinase reporter gene ( ttk ) using [ 18 F]-FHBG for PET
imaging [73,74]. Due to the risk of possible teratoma formation, the ttk gene
also acts as a ganciclovir-sensitive “suicide gene” in response to ganciclovir
therapy that can be used to kill off all implanted cells [72]. The NIS expres-
sion system capitalizes on a highly tissue-specific membrane transporter
capable of exchanging Iodine ( 124 I) or pertechnetate (technetium-99m [ 99m Tc])
for intracellular sodium. Using this system in cardiac-derived stem cells,
ectopic NIS expression has been visualized in the heart with minimal back-
ground signal originating from tissues (thyroid, stomach, salivary glands)
that endogenously express this symport gene [74].
Cardiac MRI offers the highest anatomic resolution of any current nonin-
vasive imaging modality. To date, MR-based imaging approaches have relied
on cell labeling/tagging with MR-active contrast agents or, more recently, use
of MR reporter genes. Both negative contrast-inducing agents (e.g., dextran-
coated iron oxide nanoparticles) and positive contrast-inducing agents (e.g.,
gadolinium chelates) have been utilized in preclinical studies as a means
to image and track stem cells [75-78]. Evolution of these contrast agents to
multimodality MRI substrates such as dextran/fluorophore-coated cross-
linked iron oxide (CLIO) nanoparticles or quantum dots conjugated with
gadolinium chelates offers added versatility and flexibility beyond early MR
contrast targets [79-81]. Antibody or antigen-conjugated MR contrast agents
further enhance the capacity to image stem cells without the drawbacks of
exogenous labeling of stem cells prior to delivery. In one particularly salient
example, a hybrid quantum dot/gadolinium lipid micelle system was devel-
oped with a VEGF (vascular endothelial growth factor) homing peptide
(cyclic RGD) that permits visualization of angiogenesis in a model using
both fluorescence and MRI [82,83].
In addition to contrast agents, MR reporter genes have been developed
to permit continuous production of a MR-compatible marker. These devel-
opments are perhaps the most compelling avenues in MRI as such report
genes can reduce or eliminate the need for exogenous contrast reagents and
their undesirable side effects. Examples of these efforts include expression
of a novel lysine-rich peptide compatible with chemical exchange satura-
tion transfer (CEST) imaging [84]; expression of magA from magnetotactic
bacteria that allows for controllable postimplantation uptake of endoge-
nous iron [85,86]; and β-gal-mediated activation of the MR contrast agent
1-(2-(β-galactopyranosyloxy)propyl)-4,7,10-tris(carboxymethyl)-1,4,7,10-tet-
raazacyclododecane)gadolinium(III) (EgadMe) via LacZ expression [87].
6.2.2.4  Imaging iPS Cell-Based Therapeutic Repair
Therapeutic application of iPS cell methodology requires optimization of tis-
sue-specific regeneration in response to injury with in vivo remuscularization
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