Biomedical Engineering Reference
In-Depth Information
staining,.or.GFP.labeling..The.myelin-deicient.Long.Evans.Shaker.rats.can.be.recovered.
by. oligodendrocyte. progenitor. cell. transplantation.. Bulte. et. al.. have. shown. the. in. vivo.
migration.and.remyelination.capacity.of.SPIO-labeled.oligodendrocyte.progenitor.cells.in.
the.spinal.cord
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.and.brain.
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.MRI.has.also.been.used.to.monitor.olfactory.ensheathing.
and.Schwann.cells.in.spinal.cord.injury
233
.and.in.demyelinated.spinal.cord.lesions
234
.by.
direct.injection.
Neural.precursor.cells.showed.beneicial.effects.in.experimental.autoimmune.enceph-
alomyelitis. (EAE),. an. experimental. model. relevant. to. human. multiple. sclerosis.
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. The.
migration. of. transplanted. PLL-Feridex-labeled. neural. precursor. cells,. which. were. dem-
onstrated.by.serial.in.vivo.MRI,.can.ameliorate.the.brain.inlammation.in.a.mouse.model.
of.EAE..The.extent.of.migration.correlated.well.with.the.clinical.severity.of.the.disease..
Stem.cells.including.bone.marrow-derived.endothelial.precursor.cells.can.be.followed.as.
delivery.vehicles.by.MRI..Transplantation.of.SPIO-labeled.cells.in.glioma-bearing.severely.
combined.immunodeicient.mice.induced.hypointense.regions.within.the.tumor.area.
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.
Histological. studies. demonstrated. expression. of. CD31. and. von. Willebrand. factors. on.
labeled.cells.that.had.iniltrated.the.tumor.mass.
Scar.formation.due.to.ischemia-induced.death.of.cardiac.myocytes.can.be.recovered.by.
infusion.or.injection.of.stem.or.progenitor.cells..Furthermore,.endothelial.progenitor.cells.
have.been.shown.to.augment.blood.low..Despite.promising.results.from.primary.clinical.
trials,.many.practical.issues.and.mechanisms.remain.highly.controversial..Visualization.
and. quantiication. of. injected. cells. within. the. injured. myocardial. tissue. obscure. under-
standing. of. mechanisms. relating. to. stem. cell. transplantation.. Kraitchman. et. al.. studied.
the. MRI. potential. of. tracking. magnetically. labeled. bone. marrow-derived. mesenchymal.
stem.cells.in.a.swine.model.of.myocardial.infarction..Intramyocardial.injection.of.2.8.to.
16 ×.10
7
.cells.was.tracked.successfully.using.a.1.5.T.MR.scanner.for.up.to.8.weeks.after.cell.
transplantation.
237
.An.extremely.high.heart.rate.and.small.tissue.are.major.challenges.in.
heart.MRI.in.small.animals..However,.Cahill.et.al..have.used.ferumoxide:polycation.com-
plexes.for.the.monitoring.of.therapeutic.muscle-derived.stem.cell.transplants.in.murine.
dystrophic.muscle.
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.Endosomal.accumulation.of.superparamagnetic.iron.oxide.resulted.
in.changes.in.the.MR.contrast.T2.and.T2*.at.the.left.anterior.wall.of.the.animals.receiving.
labeled. transplants. in. correlation. with. histological. images. obtained. by. conventional.
microscopy..Furthermore,.magnetically.labeled.adipose.stem.cells,
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.mesenchymal.stem.
cells,
240
. human. amniotic. luid. stem. cells,
241
. and. embryonic. stem. cells. have. been. tracked.
successfully.in.heart.disease.models.in.small.animals.by.MR.techniques.
The.ability.to.track.hematopoietic.stem.cells'.migration.would.provide.new.insight.into.
the. mechanisms. of. cellular. engraftment. after. hematopoietic. stem. cell. transplantation..
Akbari. et. al.. have. used. two. commercially. available. FDA-approved. SPIO. nanoparticles,.
ferumoxide.and.protamine.sulfate,.for.in.vivo.homing.of.human.CD34+.cells.in.irradiated.
mice.. They. found. that. the. intravenous. injection. of. 0.5-1.5. ×. 10
7
. labeled. CD34+. cells. can.
decrease.MR.signal.intensity.in.bone.marrow.at.24.and.48.h.after.injection.
242
.The.same.
results. have. been. reported. by. Daldrup-Link. et. al.. for. cord.blood-derived. hematopoietic.
stem.cells.using.ferumoxides.
243
Unlike. quantum. dots,. iron. is. naturally. present. in. the. human. body. in. the. amount. of.
almost.4.g.in.an.average.adult..Ferumoxides,.the.only.pharmaceutical-grade.MRI.contrast.
agents,.are.completely.biodegraded.in.approximately.2-4.weeks..The.iron.core.of.ferumox-
ide. is. recycled. into. the. normal. blood. poll,. including. hemoglobin.
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. Thus,. the. approved.
contrast. agents. can. be. used. in. clinical. cellular. therapy. trials.. However,. the. translation.
from.experimental.studies.to.clinical.applications.requires.much.better.preparation.and.
perseverance.to.be.evaluable.in.phase.I.clinical.trials.
