8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
1/21
Cord Blood: Between ES andAdult Stem Cells?
CRT 2006
Roger J. Laham, MDRoger J. Laham, MDDirector, Angiogenesis Research Center Director, Angiogenesis Research Center
Assistant Director, Interventional CardiologyAssistant Director, Interventional Cardiology
Director, Basic Angioplasty ResearchDirector, Basic Angioplasty ResearchAssociate Professor of MedicineAssociate Professor of MedicineBIDMC!arvard Medical "choolBIDMC!arvard Medical "chool
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
2/21
Conflict of Interest StatementConflict of Interest Statement
Roger Laham, MD
I have no real or apparent conflicts of interest to report.
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
3/21
Lost in #ranslation$$
% Despite decades of research and !ears ofclinical trials" therapeutic an#io#enesis$
m!ocardial re#eneration remains elusi%e
% Bench" preclinical" and earl! clinical resultsare incredi&le" onl! to crash in later sta#es
of de%elopment
% '('s" )E('s as proteins or #enes" s*eletalm!o&lasts" &one marrow cells" +and ,stem
cell-
Kenneth Chien
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
4/21
&hy the fail'res and disappointments$
% An#io#enesis$m!o#enesis are comple. processesand multiple steps are needed for functionall!
si#nificant an#io#enesis
% Tar#et population is older" ha%e endotheliald!sfunction" h!percholesterolenemia" and scarred
m!ocardium" /uite different from commonl! used
animal models 1u%enile" normocholesterolenemic"
normal endothelial funtion
% Deli%er!" a#ent handlin#" +% 3utcome measures
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
5/21
(lder Age
4 6 25C
7
0hours
8on97
)E('
2:s
4 6 25C
7
0hours
8on97
)E('
2:s
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
6/21
Ad'lt !yperChol Animals
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
7/21
"o )hy Cord Blood$$
% Adult stem cells ma! ha%e limitedtransdifferentiation potential and ma! &e
limited &! a#in# process
% Em&r!onic stem cells while trul! promisin#carr! an ethical 8euse
% Cord &lood deri%ed stem cells ma! &e morecapa&le of transdifferentiation than adult
cells and ma! carr! less sti#ma???
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
8/21
*ot a ne) idea, Crisa, Blood +
% As compared )ith ad'lt -one marro), cord -lood
progenitor cells have -een sho)n to have a higher proliferative and selfrene)al potential
% BM reconstit'tion )ith cord -lood led to engraftment ofcord -loodderived progenitors of the endothelial lineage,)hich )ere recr'ited to form ne) -lood vessels e/tending
from the thymic implant into the s'rro'nding mo'se tiss'e
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
9/21
Cord -lood derived progenitor cells% 0m-ilical cord -lood contains circ'lating stemprogenitor cells
e1'al or e/ceeding -one marro) and greatly s'rpassing ad'lt
peripheral -lood% "tem cells from cord -lood e/pand longer in c'lt're, prod'ce larger
hematopoietic clones in vitro, and have longer telomeres
% Cord -lood also contains mesenchymal progenitor cells capa-le of
differentiating into marro) stroma, -one, and m'scle, and theimmat'rity of neonatal cells compared )ith ad'lt cells doestranslate into greater cell plasticity )ith a com-ination of f'sionand transdifferentiation
% $$$$Imm'nogenicity
Le Ricousse-Roussanne, Cardiovascular Res 2004 Pesce, Circ Res 2003
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
10/21
2/perimental Design
34 "CID*(D mice 34 56B mice
LAD Ligation MI model
"ham In7ection Cord -lood Monon'clear
In7ection 8+/+49:
"acrifice at 9 and +; days
!emodynamics, ##C staining, Imm'nohistochemistry 8!*A and!LA+ antigen Colocali5, -5>5, #>5-eta:
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
11/21
!emodynamics
0
10
20
30
40
50
60
70
80
90
100
AOP LVP LVEDP
m m H g
control
treatment
;
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
12/21
CD=;? Cord -lood in *(D"CID mo'se MImodel
Control#reatment
0
500
1000
1500
2000
2500
3000
+ dp/dt max - dp/dt max
m m H g / s e c
control
treatment
;
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
13/21
Cord -lood in mice@ ##C staining
Control #reated
# # C s t a i n i n g A M I
Control #reatment
P4.44
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
14/21
!istologyCONTROL TR!T"NT
H#
Trichrome
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
15/21
CD=+ "taining
$%&.&&&'
Treatment Control
C ( ) ' + c e l l s / h p f
Treatment
Control
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
16/21
&hat are the potential mechanisms
% ;h!sical: 7ncrease wall thic*ness
;re%ention of ne#ati%e remodellin#
'i&rosis with tetherin# of in1ured wall% Biolo#ic: 7nflammation or a#ent induced an#io#enesis
and re%asculariation
Repopulation of dama#ed cells
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
17/21
Remodelling@
NC MI-C NC-TX MI- TX
TIMP-2
MMP-2
MMP3
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
18/21
!LA#*I!*A
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
19/21
Imm'notolerance
% Same results seen in SC7D983D and ')B
and duplicates pre%ious data in rats with noecidence of re1ection at 5 months
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
20/21
&or in progress
% @ar#e animal model of porcine and umanCord &lood implantation
% CRE9@o. recom&ination to assess the
contri&ution of fusion %s=Transdifferentiation
% Seedin# cord &lood on decellularied matri.and scaffolds to in%esti#ate role of
e.tracellular milieu
% Stud!in# %arious su&populations of cord&lood and cord elements
8/17/2019 Cord Blood SC-A0915 RogerLaham CORDBLO Wed
21/21
Colleag'es Colla-orators
The First Affiliated Hosital of !un
"at-sen
#uifu $u
%niversit& of 'ue(ec
Pierre 6oisine
Incheon, Eorea
"e'ng 0n Lee
Roger Laham Michael -ennett
Jian Li Alicia Maclei
Joanna &yr
Top Related