Biomedical Engineering Reference
In-Depth Information
organs.or.acquire.normal.function.again..Perhaps.it.is.here.that.modern.stem.cell.technol-
ogy.follows.the.ancient.mythology,.and.in.few.years.we.may.see.yet.another.miracle.of.the.
application.of.scientiic.knowledge.
The.increase.in.average.life.expectancy.leads.to.an.aging.society.where.human.beings.
are.particularly.susceptible.to.progressive.cell.destruction.and.irreversible.loss.of.tissue.
function,.and.ultimately.degenerative.diseases..Regenerative.medicine.is.expected.to.play.
a.powerful.role.in.this.scenario.in.the.future..It.promises.to.develop.effective.therapies.to.
repair.the.underlying.pathobiology.and.restore.the.native.cellular.architecture.and.organ.
function. through. the. use. of. natural. (e.g.,. living. cells). or. synthetic. materials.. The. term.
regenerative medicine
,.coined.by.William.A..Haseltine.in.2000,.subsumes.pharmacotherapy,.
tissue.engineering,.gene.therapy,.and.cellular.therapies,.including.stem.cells.
Cells. have. a. central. role. in. tissue. regeneration,. and. understanding. the. principles. of.
cell. biology. contributes. to. the. decoding. of. tissue. homeostasis. and. repair. mechanisms.
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.
Somatic,.adult,.or.embryonic.stem.cells.are.the.main.candidates.in.this.scenario..In.addi-
tion,. versions. of. embryonic-like. cells,. called. induced. pluripotent. stem. cells,. have. been.
recently.used.for.this.purpose..These.cells.are.reprogrammed.from.adult.cells,
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.and.can.
be.obtained.very.easily..Stem.cells.provide.the.active.ingredient.of.regenerative.therapy,.
as.they.can.continually.self-regenerate.and,.under.the.right.conditions,.differentiate.into.
specialized.cell.types.to.form.new.tissues.
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Specialized.applications.of.therapeutic.repair.are.being.explored.with.the.use.of.stem.
cell-based. platforms. and. their. cell. progeny. derivatives. for. cell. therapy. of. degenerative.
disorders.
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.However,.regeneration.of.organs.from.stem.cells.is.a.complex.continuous.pro-
cess,. and. the. ability. of. transplanted. cells. to. migrate. from. the. transplantation. site. to. the.
lesioned. area. and. to. survive,. differentiate,. and. replace. lost. cells. or. produce. growth. fac-
tors. and. cytokines. is. crucial. for. long-lasting. tissue. regeneration.
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. Stem. cells. are. placed.
in.tissue-speciic.microenvironments.that.nurture.cells.and.maintain.tissue.homeostasis..
This. microenvironment,. called. a. niche,. is. essential. to. maintain. a. balance. between. stem.
cell. quiescence. and. activity.
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. Understanding. the. biological. signals. that. result. in. stem.
cell.homing.and.regeneration.of.target.tissue.is.a.key.factor.in.successful.stem.cell.ther-
apy..Constant.observation.of.tissue.regeneration,.at.the.single-cell.level,.would.markedly.
improve. our. knowledge. about. the. underlying. cellular. mechanisms. and. is. essential. for.
preclinical.studies.in.rodents.and.potentially.in.humans.
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Conventionally,. the. study. of. stem. cell. engraftment. was. mainly. conined. to. invasive.
and.irreversible.histological.and.molecular.biology.techniques,
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.which.truly.represent.the.
problem.of.“inding.a.needle.in.a.haystack.”.Invasive.biopsies,.needed.to.pursue.histologi-
cal.techniques,.can.cause.tissue.damage.and.are.also.ethically.questionable,.as.these.can.
result. in. iatrogenic. complications.. Additionally,. the. accuracy. of. conventional. histology.
and. molecular. biology. as. the. predominant. ex. vivo. assessment. techniques. depends. on.
adequate.sampling..For.example,.if.the.transplanted.cells.are.engrafted.in.a.large.organ,.
such.as.the.brain,.the.biopsy.might.sample.a.part.of.the.organ.where.the.cells.were.not.
engrafted.and.the.result.would.be.a.false.negative..Even.if.this.approach.is.justiied.based.
on.the.use.of.a.genetic.marker,.such.as.bromodexyuridine.(BrdU),.repeated.biopsy.to.follow.
the.cell.is.technically.almost.impossible..Therefore,.histological.studies.based.on.biopsy.
have.considerable.limitations.for.cell.tracking,.and.it.is.impossible.to.use.these.techniques.
for.cell.monitoring.in.stem.cell.therapy.settings.
Another. major. limitation. of. conventional. histological. and. molecular. biology. assess-
ments.is.that.they.are.very.poor.in.live.cellular.detection,.as.they.lack.application.in.living.
organisms,.and.thus.cannot.provide.deep.tissue.information.for.stem.cell.homing..Speciic.
imaging.techniques.therefore.are.a.pressing.need.in.biomedical.sciences.to.enhance.the.