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I Dewa Ngurah Agung Satriawan

 ëtem cell
Defined by itë capability both to ëelf-renew and to
generate multiple differentiated progeny
 =iëtory
ï 1908 uëëian =iëtologiët purpoëeë term Stem Cell
ï 1968 Gone marrow tranëplant between two ëibling ëucceëfully
treat SCID
ï 1978 =ematopoetic ëtem cell diëcovered in human cord blood
ï 1981 uouëe embrionic ëtem cell derived from inner cell maëë
ï 1990 Œindvall et al tranëplant adrenal ʹfetal SN to PD patient
ï 1992 Neural ëtem cell waë cultured in vitro aë neuroëpherë
ï 1998 èameë thompëon and coworker derive the fiët human
embrionic ëtem cell
ï 2009 ÿim „
 create "induced pluripotent ëtem cellë" (iPS)
ï àhere are two main broad typeë of ëtem cellë
Embrionic Stem Cellë and Adult Stem Cellë

Embryonic ëtem cellë are located in blaëtocyëtë
and adult ëtem cellë are located in adult
tiëëueë
ï àhe potential to differentiate into different cell
typeë of the ëtem cell are devided to
àotipotent,Pluripotent,uultipotent,Unipotent
 ]

]
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 Introduction
ï STROKE is one of the major causes of death and
disability among the adult population across the world
in general and in the US in particular. In spite of the
extensive research in the field of stroke biology, there is
little effective treatment for a completed stroke.
ï Neurons are the functional units of the nervous system,
their damage and/ or loss results in the impairment of
brain function. Consequently, for adult tissue repair the
damaged neuronal population needs to be restored,
either by repair or replacement.
 ï In general, stem cell therapy for stroke can be divided in two strategies: the
transplantation of precursors or stem cells, and the stimulation of endogenous
neural progenitor cells. The transplanted cell strategy is based on the
replacement potential expecting that these cells could migrate, differentiate and
integrate, and may be transplanted locally or administered intravenously. The
stimulation of endogenous neural progenitor or stem cells locally would
represent a strategy to promote regeneration of injured brain (Taupin, 2008).

   
        
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checkpoint

ºerspectives of Stem Cells From Tools for Studying Mechanisms of Neuronal Differentiation towards Therapy, Henning
Ulrich, Springer Science+Business Media B.V. 2010,
!  "#$%&'()Cellular ëignaling in neural ëtem cellë implicationë for reëtorative neuroëurgery
 ]

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Identification and Characterization of Neural Progenitor Cellë in the Adult uammalian Grain, Springer 2009
Transplantation of precursors or stem cells
for Stroke
ï ueëenchymal ëtem cell (uSC)
ï Immortalized Neural Stem Cellë
ï Endogenouë Enhance Progenitor
ï Somatic cell nuclear tranëfer (SCNà)
ï Induced Pluripotent Stem Cell (IPS)

Stroke ecovery with Cellular àherapieë, =umana
P,2008

0 
ï  Our findingë indicate that intravenouë injection of ex vivoʹcultured autologouë uSCë ië a ëafe
and feaëible method of treatment for iëchemic ëtroke
Doubleblind ëtudieë with larger cohortë are
needed to reach a definitive concluëion regarding the efficacy of uSC therapy
In addition, further
ëtudieë are needed to determine which ëtroke patientë ëhould undergo tranëplantation, becauëe the
location, ëeverity, and chronicity of the ëtroke and the adequacy of blood ëupply will likely affect the
efficacy of uSC therapy

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ï àhe capacity of adipoëe-derived ëtem cellë (ASCë)

for neural differentiation haë been the ëubject of
a number of recent inveëtigationë, ASCë for
neuronal therapieë, particularly for recovery from
cerebral iëchemia
ï Neuron induced ASCë can ëurvive after
ëtereotactic tranëplantation into the dentate
gyruë of the intact mouëe brain, and can ëurvive
at leaët 12 weekë after tranëplantation
ï Unfortunately, very lack of trialë for ëtroke were
done

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 Can be Obtained
ï 1
the iëolation of a homogeneouë
population of uSCë reëultë from
the adherence of ëtromal cellë to
plaëtic, which depleteë
hematopoietic progenitorë and
other cellë

ï 2
culture cocktailë uëed to induce
neuronal differentiation generally
require agentë ëuch aë retinoic or
valproic acid, growth factorë,
antioxidantë, demethylating agentë,
or compoundë that increaëe
intracellular cAuP

ï 
Genetic inducerë of neuronal
differentiation, including !



and ! 
àhe Potential of Adipoëe-Derived Adult Stem Cellë aë a Source of Neuronal Progenitor Cellë º 
„  



 

2005
àhe Potential of Adipoëe-Derived Adult Stem Cellë aë a Source of Neuronal Progenitor Cellë º 
„  



 

2005
 

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Stroke It ië not clear, however, which are the progenitor cellë that give riëe to theëe ͞neural͟
cellë

Umbilical cord blood cellë and brain ëtroke injury bringing in freëh blood to addreëë an old problem,  

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ï iluoreëcent Image
ï Decreaëeë the inflammatory reëponëe after ëtroke

Stroke ecovery with Cellular àherapieë, =umana
P,2008

|

iuture ëtudieë will be neceëëary to aëcertain the predominant mechaniëm of action of the cellë and the
potential therapeutic window in humanë

eëtorative Neurology and Neuroëcience (2009) 41ʹ54 41 Syëtemic delivery of umbilical cord blood cellë for ëtroke therapy A review
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ï àhe ŒGS-Neuronë are derived from a cell line initially developed in the mid-
1980ë and manipulated further in tiëëue culture and in animal modelë by
ëeveral reëearch teamë from the late 1980ë onward
ï originate from a human teratocarcinoma found in a 22-year-old cancer
patient
ï treating the parent cellë with retinoic acid, a biological agent known to
induce the maturation of cancer cellë into their normal-looking,
noncancerouë equivalentë
ï uultipotent neural ëtem cellë
ï Phaëe I ,Phaëe II it ië inferred that ëtereotactic cell implantation of
immortalized multipotent neural ëtem cellë, derived from a tumor cell line,
ië relatively ëafe and devoid of delayed cell-related adverëe effectë the
tranëplanted cellë ëurvive in vivo and ëome patientë that received cell
tranëplantë ëhowed motor and cognitive improvementë
http www
neuroëurgery
pitt
edu
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ï Granulocyte-colonyʹëtimulating factor (G-CSi) ië a growth factor that
actë on hematopoietic ëtem (CD4) cellë to regulate neutrophil
progenitor proliferation and differentiation
ï G-CSi exhibited neuroprotective and regenerative activity, including
recruiting neural progenitor cellë, reducing cerebral edema,
improving ëurvival, and enhancing ëenëorimotor and functional
recovery

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Divide into 1
àherapeutic clone

2
eproductive cloning
Uëing an ovum with a donor nucleuë
the nucleuë, which containë the organiëm'ë DNA, of a
ëomatic cell (a body cell other than a ëperm or egg
cell) ië removed and the reët of the cell diëcarded
At
the ëame time, the nucleuë of an egg cell ië removed

àhe nucleuë of the ëomatic cell ië then inëerted into
the enucleated egg cell

ï ÿnown aë =uman embrionic ëtem cell (hESC)
ï Preëident Guëh '/A . BNovember 26, 2001
limited federal tax dollarë for embryonic ëtem cell
ï 2009 approved by iDA
ï Current Spine Injury àrial (GNOPC1) by Geron Inc
ï =uman ëtroke trial Not yet
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ï Œateët reëearch in Stem Cellë

ï claim to be the 'ultimate ëtem cell ëolution
ï Pluripotent ëtem cellë artificially derived from a non-
pluripotent cell, typically an adult ëomatic cellë, by
inducing a "forced" expreëëion of certain geneë

ï IPSCë were firët produced in 2006 from mouëe cellë and
in 2007 from human cellë
ï Gecauëe viruëeë are uëed to genomically alter the cellë,
the expreëëion of cancer-cauëing geneë or oncogenë
may potentially be triggered
ï in April 2009, the group of Sheng Ding in Œa èolla,
California, could ëhow that the generation of iPS cellë
waë poëëible without any genetic alteration of the adult
cell via poly Arginine anchorë call Protei n Induced
Pluripotent Stem Cell (pIPS)
ï It waë claim Save and ëtable
ï uAààES AISING iPS CEŒŒ SAiEà AND Eà=ICS,1,2
ï =uman ëtroke àrial Not yet eëtabliëh
  
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ï Previouëly, a clonal human neural ëtem cell line (=G1
i) that had been
immortalized by a retroviral vector encoding the v-@  
„„ 



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line ëhowë multipotent capacity to differentiate into
neuronë and glial cellë and ameliorate neurological deficitë in animal modelë
of ëtroke , Parkinëon͛ë diëeaëe , =untington͛ë diëeaëe , and lyëoëomal
ëtorage diëeaëe
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ï àhe ëtable immortalized human NSC lineë
deëcribed here can be expanded readily and
provide a renewable and homogeneouë
population of neuronal and glial cellë, and
they will provide moët valuable meanë for
future ëtudieë of fundamental queëtionë in
developmental neurobiology, cell and gene
therapieë, and reëearch and development of
new drugë and new treatment

ï In concluëion, i human NSC line can be
induced to differentiate into neuronë and glial
cellë in vitro and in vivo and haë a potential to
produce ëeveral neuroprotective factorë,
including NGi and GDNi
àhe preëent ëtudy
demonëtrateë that i human NSC cell line ië
not only a uëeful tool for the ëtudieë of
neurogeneëië but alëo aë a renewable cell
ëource for the ëtem cell-baëed cell therapy in
the CNS diëeaëeë
 Cell àracking and Imaging
ï uI haë been the mainëtay for tracking implanted
ëtem cellë in vivo (7-14 à)
ï Superparamagnetic particleë, ëuch aë iron oxide
nanoparticleë, have been the moët commonly uëed
cell-labeling ëubëtanceë ëo far
(SPIOë),(USPIOë),(uPIOS)

ï PEà and SPECà with radiolabelling
ï uicroCà aë a New uethod for in vivo Cell àracking
ï uax ëpatial reë Conventional mCà 0
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