Biomedical Engineering Reference
In-Depth Information
in.vivo.study.of.cells.that.is.crucial.for.the.development.of.cellular.medicine.
8
.Developments.
of.new.imaging.technologies.have.long.played.a.pivotal.role.in.the.progress.of.biomedical.
sciences,.as.shown.by.the.number.of.Nobel.Prizes.awarded.for.this.progress:.for.phase-
contrast. microscopy. (1953),. computer-assisted. tomography. (1979),. electron. microscopy.
(1986),. scanning. tunneling. microscopy. (1986),. nuclear. magnetic. resonance. spectroscopy.
(2002),.magnetic.resonance.imaging.(MRI).(2003),.and.gene-targeted.imaging.with.green.
luorescent.protein.(GFP).(2008).
A.stem.cell.has.the.potential.to.differentiate.into.other.cell.types.and.proliferate,.survive,.
and.self-renew.over.a.long.period.of.time..Due.to.the.lack.of.a.speciic.culture.system.that.
allows. stem. cell. growth. for. the. long. term,. in. vitro. imaging. is. not. suficient. to. provide.
reliable.information..Furthermore,.most.stem.cell.characteristics.depend.on.their.cell-cell.
contact.and.the.three-dimensional.(3D).structure.of.their.niche..Although.there.are.some.
techniques.for.in.vivo.cell.imaging,.such.as.genetic.markers,.stem.cell.detection.requires.
some.speciic.considerations..Stem.cells.are.rare.in.tissues,
10,11
.so.unlike.observing.a.num-
ber. of. homogeneous. cells. (such. as. in. T. cell. imaging),
12
. a. strong. signal. of. higher. resolu-
tion.is.likely.to.be.required.for.the.detection.and.distribution.of.stem.cells.within.tissues.
and.organs,.especially.at.the.single-cell.level..In.addition,.study.of.different.stages.of.cell.
maturations.and.the.intrinsic.characters.of.stem.cells.can.be.carried.out.only.by.using.a.
combination.of.molecular.markers,
13
.and.therefore.an.imaging.modality.that.allows.multi-
color.labeling.and.detection.is.crucial..High.costs.for.generating.enough.data.to.carry.out.
a.reliable.statistical.analysis.that.is.extremely.time-consuming.are.another.requirement.
Of.course,.in.this.scientiic.court,.these.life-saving.ideas.and.imaginations.are.innocent,.
and. our. own. creativity. is. main. accused.. For. example,. when. Anton. van. Leeuwenhoek.
discovered. sperm. in. 1678. with. his. microscope.. He. originally. believed. them. to. be. par-
asitic. animals. living. within. the. semen. (hence. the. term.
spermatozoa
,
meaning. “sperm.
animals”),. but. he. later. came. to. believe. that. each. sperm. contained. a. preformed. embryo..
Nicolas. Hartsoeker,. the. other. codiscoverer. of. sperm,. drew. a. picture. of.
what he hoped to
ind
:.a.preformed.human.(“homunculus”).within.the.human.sperm.
14
.This.story.indicates.
that. researchers. tend. to. see. what. they. expect. to. ind.. The. brain. can. ilter. and. interpret.
information. in. a. way. that. matches. with. its. own. inclinations.. This. means. that. the. right.
data.can.result.in.inappropriate.or.distorted.conclusions,.and.vice.versa..Thus,.it.is.almost.
impossible.to.understand.the.complex.continuous.processes.involved.in.organ.regenera-
tion. through. stem. cells. if. the. analyses. rely. on. individual. snapshots. of. cell. populations..
Constant,.accurate,.and.speciic.scientiic.observation.with.high-resolution.sophisticated.
techniques.is.indispensable.
Determining. the. fate. of. a. particular. cell. population. within. a. heterogeneous. environ-
ment. is. the. common. goal. of. all. cell. tracking. assays.. Speciic. labels,. known. as. contrast.
agents,. are. necessarily. used. to. highlight. and. distinguish. a. particular. cell. among. other.
cells.within.tissue..Along.with.the.development.of.new.imaging.modalities,.use.of.better.
contrast. agents. and. tracers. has. led. to. enhanced. sensitivity. (“more. bang. for. the. buck”),.
increased. cellular. uptake,. and. has. enabled. the. modulation. of. energy. (light,. sound,. and.
electron.beams)..Although.in.past.decades.major.progress.was.seen.in.the.development.of.
tracking.agents,.nanoparticles.form.an.important.class.of.materials.with.unique.features.
that. make. them. highly. suitable. for. biomedical. imaging.. They. can. dramatically. amplify.
signal.changes.when.used.as.contrast.agents.in.magnetic.resonance.imaging,.exhibit.sur-
face.properties.that.improve.cell.entrance.and.selective.uptake.by.speciic.cells.(e.g.,.mac-
rophages),.and.possess.unique.chemical.properties.that.make.them.visible.(e.g.,.quantum.
dots.in.luorescent.imaging)..Nanoparticles.are.now.widely.used.with.many.commercially.
available.preparations..Several.of.these.are.being.used.clinically.and.have.undergone.FDA.
