Adam Lerman Date: May 11

Ghrelin promotes the diferentiation of human embryonic stem cells in

infracted cardiac microenvironment
Reference: Meijuan Gao, Jin Yang, Guoqiang Liu, Rui Wei, Lin Zhang, Haining Wang, Guang Wang, Hongwei
Gao, Guian Chen, Tianpei Hong, Ghrelin promotes the dierentiation o human em!r"oni# stem #ells in
inar#ted #ardia# mi#roen$ironment, %eptides, &olume '(, )ssue *, +pril *,-*, %ages '.'/'.0, )112 ,-03/
0.4-, -,5-,-36j5peptides5*,-*5,*5,,35
Background:
Human em!r"oni# stem #ells 7h81C9s: are deri$ed rom inner #ell mass o !lasto#"st o em!r"os, whi#h
are used or in vitro fertilization and em!r"oni# donations5 h81 #ells are used !e#ause o their sel renewing
a!ilit" and their pluripoten#" to dierentiate into germ la"ers5 h81C9s are used or regeneration o and organ
regeneration o tissues, li;e or m"o#ardial regeneration to treat irre$ersi!le heart injuries5
Ghrelin is an endogenous ligand or the growth hormone se#retagogue re#eptor to promote the release o
growth hormone5 )t is un#lear is h81C9s #an indu#e m"o#ardial generation !" ghrelin ater in vivo engratment
into the m"o#ardium5
What was done:
+dult male 1prague/<awle" rats that were eight wee;s old were used5 The h81C9s were #ultured on "/
irradiated mouse em!r"oni# i!ro!last eeder la"ers5 The rats were indu#ed with m"o#ardial inar#tion 7M): !"
the ligation o the let anterior des#ending #oronar" arter" 7L+<:5 The" used one millions undierentiated
h81C9s and inje#ted them into the hearts5 The Mi animals transplanted with h81C9s were put into two treatment
groups= the su!#utaneous inje#tions o ghrelin or the phosphate !uered solution 7%>1:5 The #ontrol group was
the sham ligation and %>15
Transthora#i# e#ho#ardiograph" was done ( wee;s ater #ell transplantation !eore the rats were
sa#rii#ed to measure the ma?imal let $entri#ular end/diastoli# 7L&<d, mm:, the end/s"stoli# diameter 7L&1d,
mm:, the #orre#tion let $entri#ular mass 7L& mass, mg: and the ra#tional shortening 7@1:5
Histo#hemi#al staining was done ( wee;s ater the rats were sa#rii#ed and ater the #ells were inje#ted5
The ma#ro se#tions were em!edded with reeAing media and were ;ept roAen at B4, Celsius5 M"o#ardial
se#tions were se#tioned at 4 mi#rometers on a #r"ose#tion5
What was learned:
The undierentiated h81C9s were grown on a eeder #ells that were #ompa#t, and were tested positi$e
or the pluirpotent mar;er al;aline phosphate 7+C%:5 The se#tions that were stained or hemato?"lin and eosin
7H8: showed that m"o#ardial #ells in an irregular shape and arrangement with m"o#ardial i!rosis was o!ser$ed
in the inra#ted area ( wee;s ater #oronar" ligation5 The histologi#al tests showed that the se#tions were
positi$e or grated #ells5
)n the ghrelin/treated group, there were D45'E o grated #ells that was positi$e or human nu#lear
antigen 7H2+:, and in the %>1 treated group there were ''5'E o grats positi$e or H2+5 This shows that
ghrelin was !enei#ial to h81C9s sur$i$al and in the dierentiation in into #ardia# progenitors in inra#ted
#ardia# mi#roen$ironment5
The heart un#tion was e$aluated ( wee;s ater h81C transplantation5 This showed that M) e?perimental
groups diered with the #ontrol groups to the #hanges in measures o @1 and L&1d5 There was no signii#ant
#hanges were ound in the let $entri#ular #orre#tion mass in the h81C/transplanted group when #ompared to
the #ontrol group5 The arti#le suggests that the $entri#ular weight were not ae#ted !" the M) model or #ell
inje#tion5
What is means:
The data shows that h81C9s #an sur$i$e and orm sta!le intra #ardia# grats in inra#ted #ardia#
mi#roen$ironment5 The heart un#tion !" using e#ho#ardiograph" showed that the engrated #ells and the
ghrelin administration were not enough to restore heart un#tion5 There is e$iden#e that ghrelin ma" pla" a role
in the regulation o #ell dierentiation during de$elopment5 Gherlin un#tions as inhi!iting #ardiom"o#"te and
endothelial #ell death, impro$ing L& d"sun#tion in humans, and attenuation the de$elopment o #ardia#
#a#he?ia !" de#reasing s"stemi# $as#ular resistan#e in rats with #hroni# heart ailure5 This stud" showed the
potential !eneit o ghrelin on h81C dierentiation into #ardia# progenitors in inra#ted #ardia#
mi#roen$ironments5