AUGUST 20,07 vor. e No. 8
INSIDETHIS ISSUE
e
@ Regen e r a t i vM e d i c i n e :
P t
Adv anci n g a t i e n C a r e
@ Labt o L i m b :C l i n i c aA p p l i ca tio n s
l
of Regenerative Medicine
@ I Vat ingt h e T r a n s i t i o n :
Hos pita B l o o dB a n k sB e g i n
l
Move to ManageTissue NEU/S
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@ Tis s ue e c a l l s r o m
F
I nit iat i o no C o m p l e t i o n
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"Mad
How Regeneratrve and
Medicine
Tissue
Management Advancing
Are Patient
Care
he fact that salamanders
can very smallpieceof tissue,halfthe size provi di ng n but strongsuppor t ive
thi
regrowa limb when it is cut off of a stamp,and by day 60 we can have threads and
thatal l owcapi l l ari es cells
andhum ans an n o t a sb a ffl e d
c h e n o u g h el l sto covera footbalfi el d,"
c l to attach,move and grow.The scaffold
researchers decades.
for Having
the saidAnthony of
Atala,MD, director the sometimesincludes layerof silicone
a
a b i l i t yo gr ow andr e p l a c e a ma g e d
t d lnstitute Regenerative
for Medicine water vaporlossand increase
to control
limbsand organs a resultof disease,
as in
at Wake ForestUniversity Winston- tear strength.
injuryor simplyold agewould revolu- N
S a l e m, . C . To createskin,the scaffoldis
ti o n i z e edic ine.
m lmprovements these havemade
like " seeded"w i th humanautol og ous
or
Foryears, fieldof regenerative
the e n g i n e e r ed na readi l y
ski e
avai l ablshel f c
al l ogeneiski ncel l ssuchas fi br oblast s
me d ic ine f oc us e d n d e v e l o p i n g
has o productusedto treata variety condi-of and keratinocytes. Thesecellsproduce
new approaches grow cells,tissues
to tions,from pressureulcersformedin pr
col l agen w el l as the pri mary ot ein
as
and organs.
Theseeffortshavemoved patients who are bedridden lacera-
to foundi n ski n,andgi veri seto con-
from academia the private
to sector, ti o n sa n dsecond-degree
burns. nl i ke
U nectivetissue.Sometimes addedto
where companres now aretryingto skintissueavailable
from cadavers, the mix are growthfactorsas well as
g ro w s ev er al
hum an s s u e si,n c l u d i n g
ti ski
e n g i n e e r ed nhasa l ongshel fl i fe. which stimulate commu-
cytokines, cell
spinalcord nerves, bladders
cartilage, Engineered alsoofferstwo other
skin Engineered differsfrom
nication. skin
and skin.Farfrom fantasy,regenerative important lt
benefits: does not transfer normal ni n that i t doesnot c ont ain
ski
is
medicine now slowlymakingits way diseases
and,if grownfrom autologous macrophages, or
melanocytes other
intothe clinic,
with variousproducts
cur- cells,is not rejected the body.
by suchas bloodvessels
structures and
rentlyavailable the market.
on Skinis engineered usingthree
by sweatglands.
mainingredients: biodegradable
a extra- Onno imnlentad tha anninoorad
Ski n r
c e l l u l amatri x(orscaffol d), l sand,i n
cel allowsfor normalphysi-
skin'sscaffold
In 1 98i, a c r udebut s u c c e s s fu ltte m p t
a some cases,substances stimulate
that processes take place,
ological to such
was madeto grow skin outside the growth.The scaffold,
often porcineor on
as vascul ari zatiandcel ldi vi s ion.
bodyto treata burnpatient.Sincethen, bovinein nature, a collagen-rich
is struc- With time, the scaffolddegrades, leav-
the ability grow skincellsin vitrohas
to ture. Undermagnification, scaffold
the ing mostlycells grown by the patient.
"
ma rkedly pr ov ed.We c a nta k ea
im would looklikea giantloofahsponge this process,
Through wherethereonce
20 AABBNews I AUG UST2007
was no skintissue,skin now exists.
an
Engineering Organ
Regenerative medicinetechnologyhasthe potentialto createa functionalneo-organusingthe
Despite impressive scientific patient'sown cellsto augmentor replace failingorgan,forexamplea bladder.
a
advances,engineeredskin is stillnot
of
the standard care."lt is a lot cheaper @ A surgeontakesa small, isolateurothelial
@ In the lab,scientists
full-thickness biopsyfrom cells(the bladder'slining)and smooth
to o b ta in adav er k int ha nto e n g i n e e r
c s the patient's bladder.
a new "
p i ec eof s k in, "s ai dA ta l a . S o ,
financially modelis not what people
the
expected." Nonetheless, thereis a
d
n i ch e r t his pr oduc t" E n g i n e e res k i n
fo .
is usedbecause you do not necessarily
Cadaveric
havea lot of skin in banks.
and keep,and
skin is hardto harvest
you haveissuesof the skin not beinga
matchto the patient,"he added.
Atalais optimistic that new advances
i n ski ne ngineer ing eon th e h o ri z o n .
ar
"Therecertainly a needfor better
is j The
@ the isolated cells
scaffold arecultured
e n g i n e er edk in.Rightno w w e a re
s andis
. separatelyfor
enjoying flrst-and second-genera-
the / severalweeks
unti l therearea
tion products, advances needto
but still ,l
sufficient quantity.
be made.Therestillis much improve-
ment to be donein terms of scarforma-
ti o n a n df eeling. "
In l e sst han15 y ear s, n g i n e e res k i n
e d
O The;eo-bladder construct is @ Scientistsensurethat
involv-
went from a mere ideato a reality implantedby the surgeon. the cellsattach and grow
properly throughout the scaffold.
inga hostof companies offeringskin
After a total of about eight week,
products. tremendous
Thishascreated the neo-bladderconstruct is
returned to the surgeonfor
momentum regenerative
for medicine, imolantation.
turn
makingmanyresearchers their 3D renderings courtesy of Tengion Inc.
attention the possibility engineering
to of
bloodvesselsand evenmorecomplex
sucnas organs.
structures can
a vein from the leg,for example, cal deviceto a more complexproduct.
be stripped its valvesand implanted
of Many prosthetic vasculargraftsare now
Blood Vessels onto the heart. impregnated with substances pro-
that
An e sti m at ed 2 m illio n
1. Ame ri c a n s Usingthe patient's
own tissueoften mote tlssueregrowth, sealed prevent
to
havea heartattackeveryYear, and as yieldsthe best post-surgical
results,
but bloodleakage Theyare
and infection.
of
a resultof the narrowing the heart's some patients may not havevessels to woven or knittedout of a poly-
typically
arteries,more than300,000individuals spare.Theymay sufferfrom extensive esterfiberor othersimilar materialthat
undergobypasssurgery vasculardisease,suchas arteriosclero- is strongandwrinkle-resistant.
Since1968,when the f irstcoronary bloodvessels
sis,which affectsseveral Althoughprosthetic grafts
vascular
bypass performed,
was successfully in theirbody,In casessuchas these, haveseveral a
applications,common
the preferred
surgicalprocedure
has the best solutionmay be to use a pros- use is aorticreplacements patients
for
involvedreplacing coronary
the artery graft.
theticvascular with aorticaneurysms. vas-
Prosthetic
with anothervesselharvested from Overthe years, grafts
vascular culargraftsare idealsolutions cases
in
body.In this procedure,
the patient's haveprogressed
from a mere medi- likethese because aorta's
the large
and CellularTherapiesProfessionals
The Magazine Transfusion
for
keepsphysicians
diameter from easily "llssue grows inside
process. and out- it.
operation replace
ing an edditional to
findingothervessels replace
to it. sidethe graft,although graftmate-
the havetriedinstead
Researchers to
The first aorticprosthetic
vascularrialis stillthere;it does not disintegrate. createa bloodvesselby seeding tubu-
a
graftsuseddecades ago havebeenmark- Thiscreates a prettydurable proce- larscaffold with muscleor endothelial
edly improved new technologies
by and dure," saidBrooks. "To the untrained cellswith limitedresults."Thereare
processes makingthem easier use
to eye it does not looklikea graftbecause some largeinternational trialson seed-
by surgeons improving chances tissuehasgrownover it "
and the ing syntheticgraftswith autologous
for a betteroutcome.With a shelflifeof aorticgraftspresents
lmplanting endothel i al l s,"sai dN erem."lt dem -
cel
abouttwo to four years,today'saortic some challenges.Patients
undergoing that you can get increased
onstrated
graftscomealready arched,followlng this procedure not normally
are healthy patency in
[opennessJ larger six
arteries
curveof the human
the natural and
aorta, and haveto survive lengthy
a and to sevenmillimeters diameter not
in but
havesewn in otherneeded
synthetic procedure
invasive where the chest is in three millimeters
as you wouldwant
vessels. materials moresupple
The are opened.
Heartfailure stroke, well
or as for a coronary
bypass."
andeasier manage,
to therebyreducing as infection, associated
are with this Nonetheless,Neremis hopeful."lt
procedure, impor-
the time of surgical an procedure. "Peoplecan surviveyears mightbe 10 yearsbeforewe havean
tant factorin decreasing
deathratesand with theseaorticgrafts,"saidBrooks. FDA-approved bloodvessel
commercial
recoveries.
improving " However,chances if you are
are that hasbeentissueengi-
substitute
you
receiving procedure area fairly
this neered.lf we hadthis, it couldbecome
sick personor old,so you might have the preferred to
substitute use in coronary
othermore serioushealthconditions." bypass Untilthen,usinga native
surgery.
Prosthetic graftsalsoare
vascular veinwill remain goldstandard."
the
usedfor otherapplications, suchas to
replace peripheral vesselsin the body, Organs
b u t th e " hol ygrai l "i s to be abl eto The onlyorganthat can regrowafter
develop prosthetic
a graftsmall
vascular injuryis the liver. dam-
Otherseverely
enoughto be usedfor thousandsof suchas hearts,
agedorgans, kidneys
coronary
bypass operationstakingplace and lungs,stillneedto be replaced
everyyear. throughtransplantation.
" lt is difficultto get the number organtransplant
The first successful
of vessels for
that are needed allthe was conducted the American
by sur-
bypasssurgeries the country
in from geonJosephMurrayin 1954.lt was a
sources. would be idealto
cadaver lt kidney from one twin to the
transplanted
Bloodleakagealsohas been havea bloodvesselsubstitute
that other,eliminating needfor immu-
the
"Earlyon the graftsneededto
reduced. w o u l db e avai l abloff the shel f,"sai d
e nosuppression.Since then,two great
be pre-clotted the patient's
in bloodso it RobertNerem,PhD,director the Petit
of challengeshaveplaguedorgantrans-
would sealitselfthroughplatelet
aggre- Institute Bioengineering Biosci-
for and plantations:
shortages rejections.
and
gation,"saidGordonBrooks, marketing Institute Technol-
enceat the Georgia of In the UnitedStates,nearly 97,000
manager BostonScientific, of
at one ogy in Atlanta. peopleare on a waitinglistto receive
the manycompanies that producepros- Althoughthesesmall-diameter
ves- an organtransplant.Lastyear,how-
grafts." Nowadays
theticvascular many they
selscan be manufactured, tend ever,fewer than29,000organswere
graftsare impregnatedwith bovinecol- to failwhen they are implanted the
in transplanted. those patients
For who
lagen,which provides "
self-sealing. body.Bloodflow decreases to thick
due are luckyenoughto receivedonated
As with engineered
skin,collagen tissuegrowingon the innerwall of the organs, lifewith the harshside effects
a
alsoencourages tissuegrowthon the smallvesselor by bloodclotscausingit of immunosuppression often liesahead.
aorticgrafts,accelerating sealing
the to occludepartially completely,
or requir- have
Forsome time scientists
22 AABBNewS I AUG UST2007
Prosthetic vascular
dreamed growinga patient's
of own patients, expected 2008.
are in grafts are commonly
o[QOn an organthat couldbe grown "Thisis groundbreaking
work used to treat aortic
-
from patientcellsand implantedwithout because will demonstrate
it in aneurysms.
fear of rejection. this dreamcametrue,
lf principle thisapproach
that
alleviate severe
it couldsignificantly the hasmeritandcanhelp
organshortage that existstoday.The thesetypes of patients," o
optimismfor growingan organwas par- saidStephen
Badylak,
tiallyderivedfrom the experience with of
MD, PhD,director
engineered skin.lf a patient's
own skin the Centerfor Pre-
couldbe grown successfully
outsidethe Testing the
clinical at
body,why not an organ? McGowanInstitutefor
Atala,a
Wake ForestUniversity's Regenerative
Medi-
urologist, one of the
Harvard-trained is cineat the University
few peoplewho hassuccessfullygrown of Pittsburgh an
and
andtransplantedfullorgan, bladder. adjunctprofessor
a the at
He first beganreconstructing
urethras Wake ForestUniversity.
andtreatednearly100 patients with this Atalaalsohasbeen
damaged urinary
channelbeforemoving to other
trying engineer
"Tubular
on to the bladder. structures
are organswith lesssuccess.
A
complex not nearly complex
but as as differs
solidorgan,likethe liver,
holloworgans you
because arerelying from the bladder thatthey needto be
in will not be ableto grow those sorts
on neryeintervention makethe oroan
to vascularized.
internally Withoutblood of complextissuesin a bioreactor
and
work," he said. vesselsthat bringin oxygenand other successf take them to a patient,
ully "
Theprocess somewhat
is to
similar the
nutrients, organdies. The in vitroenvironment,
said Badylak.
thatof engineering A smallpiece
skin. "The problemsyou encounter
when to is
according Badylak, stillsignificantly
of the bladder takenfrom the patient,
is tryingto grow a relatively
simpletissue differentthanthe one seen in vivo.
and
andurothelial smoothmusclecells likeskin or bladder different
are than "A bioreactor very artificial; do
is we
are culturedbeforebeingseededinto those you face when you try to grow not reallymimicthe in yiyostate,and
shaped a hollowbladder.
a scaffold like an organllkeliver,kidneyor heart,"said therefore do not get the same sort
we
takesfrom six to eight
Growinga bladder Badylak."With more complexorgans of spatial of
organization the tissue," he
weeks.Afterwards, eqgineered
the blad- you haveliterally to
everything worry said.Badylakhopesthat with a change
der is implanted the patient.
into about- the vascularsystem,the inner- of strategy
that includes tryingto grow
Bladders
engineered vrlrohavebeen
rn vationof muscles, lymphatics."
the organsin vivo,there are good chances
with some success
usedin oatients and Sk i na n d b l adder thi nti ssues
are of growingan organin the next 25
beingtestedin children
arecurrently with with a coupleof celltypes,which can years.
spinabifidaandadultswith spinal
cord be grown in a bioreactor.
However, Atala,who worked 17 yearsin devel-
Thesepatients
injuries. tendto havespas- more complexorgansnot
developing that
opi ngthe bl addetacknow l edges
The muscular
modicbladders. constant growingthe organcells
only requires thereare futurechallenges believes
but
spasmsresultin bladders
with verythick but alsothe nervesand bloodvessels in pursuing roadahead."lt is a mat-
the
which decreases blad-
wall muscles, the insideit that are critical its survival.
for ter of tryingto get aroundthe problems
and
ders'elasticity createsincontinence. To makethingsmore difficult,
cells and not givingup," he said." l am a
The bladder
developed Atalaand
by from otherorgans,
suchas those from practicingsurgeon, when you see
so
hiscolleagues beencommercialized the heartand liver,
has stillcannotbe suc- patients you
that needthis technology
by Tengion. of
Results Phasell trials,in grown in the lab.
cessfully would rathernot give up. You don't for-
will
whichthe bladder be testedin 20 "My personal
opinionis that we get aboutthe patients."&l
The Magazinefor Transfusionand CellularTherapiesProfessionals 23