Biomedical Engineering Reference
In-Depth Information
2.9 CellTrackinginStemCellTherapy
Quantum. dot. imaging. holds. great. promise. as. a. competent. agent. for. tracking. stem. cell.
fate.with.single-cell.resolution.while.allowing.quantiication.of.exact.cell.numbers.at.any.
anatomic.location,.which.is.particularly.of.interest.in.cell-based.therapies..Accordingly,.in.
a.study.performed.by.Rosen.et.al.,
112
.human.Mesenchymal.stem.cells.(MSCs).have.been.
loaded.by.red.emission.QDs.for.identifying.the.spatial.distribution.of.cells.following.their.
transplantation.into.a.canine.ventricle.on.an.extracellular.matrix.scaffold..Despite.the.high.
levels.of.autoluorescence.in.the.cardiac.milieu,.individual.QD.signals.have.been.clearly.
detected.in.histologic.sections.for.up.to.8.weeks..Besides,.some.of.the.cells.had.developed.
an.endothelial.phenotype,.which.represented.the.in.vivo.compatibility.of.QDs.with.stem.
cell. differentiation. potential.. In. another. set. of. experiments,. QD-hMSCs. committed. to. a.
cardiac. lineage. in. vitro. have. been. delivered. into. the. canine. heart. on. a. patch. using. the.
ventricular.defect.model..It.was.shown.that.QD-containing.cardiogenic.cells.differentiated.
into.mature.myocytes.with.normal.sarcomere.spacing.
113,114
.The.biodistribution.of.intrave-
nously. administered. QD-labeled. MSCs. into. a. SCID. nude.mice. also. has. been. tracked. as.
they.localized.into.the.liver,.lung,.and.spleen.
115
The.inherent.long-term.luorescence.intensity.in.QDs.permits.both.in.vitro.and.in.vivo.mon-
itoring.of.stem.cell.survival,.localization,.and.differentiation,
111,115-118
.which.is.critically.needed.
in.the.ield.of.regenerative.medicine..Arginine-glycine.aspartic.acid.(RGD)-conjugated.QDs.
have.been.used.for.labeling.of.hMSCs.during.self-replication.and.multilineage.differentia-
tion.into.adipogenic,.osteogenic,.and.chondrogenic.cells..The.study.demonstrated.that.during.
the.test.period.of.22.days,.nanoparticles.did.not.adversely.affect.cellular.viability.and.pro-
liferation..Additionally,.QD-labeled.cells.had.similar.differentiation.potential,.as.evidenced.
by.the.expression.of.matrix.biosynthesis.markers,.compared.to.unlabeled.cells.of.the.same.
subpopulation.
116
.Similarly,.in.a.recent.experiment.by.Yukawa.et.al.,.adipose.tissue-derived.
stem.cells.(ASCs).labeled.with.negatively.charged.QDs.emitting.red.light.of.655.nm.wave-
length.also.retained.their.multilineage.potential.
119
.In.an.attempt.to.detect.cell.fusion.events.
in.vitro,.Murasawa.et.al.
120
.designed.a.coculture.system.that.consisted.of.both.labeled.human.
endothelial.progenitor.cells.(EPCs).and.a.rat.cardiac.myoblast.cell.line.(H9C2)..Through.the.
use.of.luorescent.microscopy.for.the.visualization.of.the.QD.signals,.the.frequency.of.cell.
fusion.was.evaluated.to.be.less.than.1%,.demonstrating.the.fact.that.transdifferentiation,.not.
cell.fusion,.is.dominant.for.EPCs.committed.to.myocardial.lineage.cells.
The.high.sensitivity.of.QDs,.along.with.virtually.an.unlimited.number.of.well-separated.
colors,. all. excitable. by. a. single. light. source,. permits. real-time. multiplex. tracking. of. par-
ticular.stem.cell.subpopulations,
121
.which.is.certainly.advantageous.because.of.the.rarity.
of. these. cells. and. the. requirement. of. multiple. markers. for. their. correct. identiication. in.
most.cases.
122
.In.order.to.conirm.the.QDs'.ability.for.in.vivo.multicolor.imaging,.murine.
embryonic.stem.cells.have.been.eficiently.labeled.with.six.different.QDs.by.using.a.pep-
tide-mediated. strategy.
117
. The. labeled. cells. were. then. injected. into. the. various. locations.
on. the. back. of. immunodeicient. mice.. With. one. single-excitation. wavelength,. six. colors,.
ranging.from.visible.to.near.infrared.(NIR),.have.been.simultaneously.detected.in.living.
mice..However,.only.the.QDs.that.had.800.nm.emitting.luorescence.could.be.imaged.up.
to.14.days,.due.to.low.tissue.absorption,.scattering,.and.autoluorescence,.as.well.as.QD800.
high-photon.penetration.depth,
24,123,124
.revealing.that.near-infrared.QDs.are.more.feasible.
probes.for.cell.tracking.within.deep.tissues.
109,125
.Despite.the.ability.of.these.luorophores.
for.deep.tissue.imaging.in.animal.models,.the.NIR.region.is.limited.to.only.4.to.10.cm.of.
tissue,
121,126
.so.that.their.clinical.use.is.only.available.for.near-surface.applications.such.as.
