Biomedical Engineering Reference
In-Depth Information
Initially. SPIO. nanoparticles. Feridex-USA. (Endorem-Europe). and. Combidex-USA.
(Sinerem-Europe),.which.are.now.FDA.approved,.were.used.for.cell.detection.in.the.retic-
uloendothelilal.system,.including.liver 245 .and.lymph.nodes. 246 .However,.in.April.2004,.de.
Vries.and.co-workers.for.the.irst.time.used.clinical-grade.SPIO.(Endorm).for.tracking.the.
autologous.dendritic.cells.of.a.cancer.vaccine.in.melanoma.patients. 247 .Using.MRI.at.3.and.
7.T,.they.showed.that.tracking.of.magnetically.labeled.dendritic.cells.is.feasible.in.humans.
for.detecting.very.low.numbers.of.cells.in.conjunction.with.detailed.patterns.of.inter-.and.
intranodal. cell. migration.. In. the. same. year,. Zhu. and. co-workers. in. Huashan. Hospital,.
Shanghai,.China,.used.Feridex.and.Effectene.(a.nonclinical-grade.lipofection.reagent).for.
tracking. autologous. neural. stem. cells. in. a. 34-year-old. man. with. brain. trauma. 248 . They.
used.a.gradient-echo.MRI.at.3.T.and.showed.that.neural.stem.cells.that.were.implanted.
stereotactically. around. the. region. of. brain. damage. moved. from. the. injection. site. to. the.
border. zone. of. the. lesion.. The. signal. intensity. disappeared. after. 7. weeks,. possibly. due.
to.cell.proliferation..In.another.study,.Toso.et.al..labeled.human.cadaveric.islet.cells.with.
ferucarbotran.(a.supermagnetic.iron.oxide.agent).and.transplanted.them.intraportally.into.
four.patients.with.type.1.diabetes. 249 .The.magnetically.labeled.islet.cells.induced.hypoin-
tense.spots.within.the.liver.and.continued.to.do.so.for.6.months.after.transplantation..The.
study.conirmed.that.SPIO.nanoparticles.are.safe.as.cell.labeling.agents.and.have.no.harm-
ful.effects.on.islet.cell.function.
2.18 Limitations
The.false.positive.effect.is.the.main.limitation.for.SPIO.nanoparticles.as.contrast.agents.in.
cellular. monitoring. after. transplantation. because. iron. aggregation. after. bleeding. in. the.
injection. site,. or. even. in. the. target. organ,. is. susceptible. to. artifact. production. in. SPIO-
induced. magnetic. resonance. images.. Contrast. transfer. from. the. dead. cells. to. nontarget.
cells,.such.as.macrophages,.is.another.source.of.the.false.positive.effect.during.imaging.
acquisition..Although.SPIO.nanoparticles.did.not.affect.the.viability.of.magnetically.labeled.
cells,. Bulte. et. al.. showed. that. Feridex. loading. can. block. mesenchymal. differentiation. to.
chondrocytes. 250 .Even.though.other.studies.do.not.prove.these.data,.the.clinical.safety.of.
SPIO.nanoparticles.when.they.are.used.for.stem.cell.research.remains.controversial.
Finally,. there. are. some. limitations. related. to. MRI. itself.. Using. MRI. in. patients. with.
pacemakers.or.implantable.cardioverters/deibrillators.is.not.possible..Patients.with.these.
devices.may.need.stem.cell.therapy.more.than.others,.and.in.this.case.we.have.to.wait.for.
more.advances.in.developing.safer.MRI.technology.or.better.implantable.devices.
References
.
1.. Nelson,. T.J.,.A.. Behfar,. and.A.. Terzic.. Strategies. for. therapeutic. repair:. The. “R”. regenerative.
medicine.paradigm.. Clin Transl Sci ,.2008,.1(2):.168-71.
.
2.. Yu,.J.,.M.A..Vodyanik,.K..Smuga-Otto,.J..Antosiewicz-Bourget,.J.L..Frane,.S..Tian,.J..Nie,.G.A..
Jonsdottir,.V..Ruotti,.R..Stewart,.I.I..Slukvin,.and.J.A..Thomson..Induced.pluripotent.stem.cell.
lines.derived.from.human.somatic.cells.. Science ,.2007,.318(5858):.1917-20.
 
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