advanced therapy in stroke,stem cells

8/7/2019 Advanced Therapy In Stroke,Stem Cells

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Advanced Therapy In Stroke

Stem Cell

I Dewa Ngurah Agung Satriawan


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stem cell

Defined by its capability both to self-renew and to

generate multiple differentiated progeny


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History

1908 Russian Histologist purposes term Stem Cell

1968 Bone marrow transplant between two sibling succesfullytreat SCID

1978 Hematopoetic stem cell discovered in human cord blood

1981 Mouse embrionic stem cell derived from inner cell mass

1990 Lindvall et al transplant adrenal fetal SN to PD patient

1992 Neural stem cell was cultured in vitro as neurosphers

1998 James thompson and coworker derive the fist humanembrionic stem cell

2009K

imet al.

create "induced pluripotentstem cell

s" (iPS)


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There are two main broad types ofstem cells:

Embrionic Stem Cells and Adult Stem Cells.

Embryonic stem cells are located in blastocysts

and adult stem cells are located in adult

tissues

The potential to differentiate into different cell

types of the stem cell are devided to :

Totipotent,Pluripotent,Multipotent,Unipotent


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Introduction

STROKE is one of the major causes of death anddisability among the adult population across the worldin general and in the US in particular. In spite of the

extensive research in the field of stroke biology, there islittle effective treatment for a completed stroke.

Neurons are the functional units of the nervous system,their damage and/ or loss results in the impairment ofbrain function. Consequently, for adult tissue repair the

damaged neuronal population needs to be restored,either by repair or replacement.


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In general, stem cell therapy for stroke can be divided in two strategies: thetransplantation of precursors or stem cells, and the stimulation of endogenousneural progenitor cells. The transplanted cell strategy is based on thereplacement potential expecting that these cells could migrate, differentiate andintegrate, and may be transplanted locally or administered intravenously. The

stimulation of endogenous neural progenitor or stem cells locally wouldrepresent a strategy to promote regeneration of injured brain (Taupin, 2008).

Stem cells in human neurodegenerative disorders,time for clinical translation?The joumal of Clinical Investigation Volume 120 ,I January-2010


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Cell Cycle

P

erspectives of Stem Cells From Tools for Studying Mechanisms of Neuronal Differentiation towards Therapy, HenningUlrich, Springer Science+Business Media B.V. 2010,

checkpoint


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Stem and Progenitor Cells in the CentralNervous System,Karger,2004

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Role of cajal


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STEM CELLS AND REGENERATIVEMEDICINE, VOLUME I,ADULTNEUROGENESIS ANDNEURAL STEM CELLS Nova Biomedical,2008


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Stroke-Induced Neurogenesis :Physiopathology and Mechanisms,Current Neurovascular Research, 2006, Vol. 3, No. 1 69


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Identification and Characterization of Neural Progenitor Cells in the Adult Mammalian Brain, Springer 2009

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Transplantation of precursors or stem cells

for Stroke

Mesenchymal stem cell (MSC)

Immortalized Neural Stem Cells

Endogenous Enhance Progenitor

Somatic cell nuclear transfer (SCNT)

Induced Pluripotent Stem Cell (IPS)

Stroke Recovery with Cellular Therapies, Humana.P,2008


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Mesenchymal Stem cell


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The capacity of adipose-derived stem cells (ASCs)for neural differentiation has been the subject ofa number of recent investigations, ASCs forneuronal therapies, particularly for recovery fromcerebral ischemia

Neuron induced ASCs can survive afterstereotactic transplantation into the dentategyrus of the intact mouse brain, and can survive

at least 12 weeks after transplantation Unfortunately, very lack of trials for stroke were

done.

Adipose-Derived Stem Cells as a Potential Therapy for Stroke

(ASCs)


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ExperimentalNeurology 2003;183(2):35566


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Can be Obtained :

1. the isolation of a homogeneouspopulation ofMSCs results fromthe adherence ofstromal cells toplastic, which depleteshematopoietic progenitors andother cells.

2. culture cocktails used to induceneuronal differentiation generallyrequire agentssuch as retinoic orvalproic acid, growth factors,antioxidants, demethylating agents,or compounds that increase

intracellular cAMP. 3. Genetic inducers of neuronal

differentiation, including Nogginand Notch


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The Potential of Adipose-Derived Adult Stem Cells as a Source of Neuronal Progenitor CellsPlast. Reconstr. Surg. 116: 1453, 2005


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The Potential of Adipose-Derived Adult Stem Cells as a Source of Neuronal Progenitor CellsPlast. Reconstr. Surg. 116: 1453, 2005


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Superparamagnetic Iron Oxide Labeling and Transplantation of Adipose-Derived Stem Cells in Middle Cerebral Artery OcclusionInjured Mice,

AJR:188, April 2007


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Hematopoetic stem Cell


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Cord Blood Cells as a Treatment for Stroke (HUCB)

Stroke : It is not clear, however, which are the progenitor cells that give rise to these neural

cells.

Umbilical cord blood cells and brain stroke injury:bringing in fresh blood to address an old problem,The Journal of Clinical Investigation Volume

114 Number 3 Au ust 2004


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Fluorescent Image

Decreases the inflammatory response after stroke

Stroke Recovery with Cellular Therapies, Humana.P,2008


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Restorative Neurology and Neuroscience (2009) 4154 41 Systemic delivery of umbilical cord blood cells for stroke therapy: A review

Animal

Future studies will be necessary to ascertain the predominant mechanism of action of the cells and the

potential therapeutic window in humans.


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Immortalized Neural Stem Cells


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http://www.neurosurgery.pitt.edu


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J Neurosurg 103:3845, 2005


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ReNeuron Group,human neural stemcell line (CTX0E03)

BMCNeuroscience 2009, 10:86


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Endogenous Enhance Progenitor


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Granulocyte-colonystimulating factor (G-CSF) is a growth factor that

acts on hematopoietic stem (CD34) cells to regulate neutrophil

progenitor proliferation and differentiation

G-CSF exhibited neuroprotective and regenerative activity, includingrecruiting neural progenitor cells, reducing cerebral edema,

improving survival, and enhancing sensorimotor and functional

recovery

Combinatorial stem cell mobilization, nature biotechnology volume 27 number 3 MARCH 2009, 252-253


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Stroke. 2010;41:927-931#

NCT00362414


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Multipotent CNS Stem Cells Are Present in the Adult Mammalian Spinal Cord and Ventricular Neuroaxis, The Journal ofNeuroscience, December 1, 1996, 16(23):75997609


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www.stemcellthera.com


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A statement from BIO world www.dundeewealth.com.


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Divide into : 1.Therapeutic clone

2.Reproductive cloning

Using an ovum with a donor nucleus

the nucleus, which contains the organism's DNA, of asomatic cell (a body cell other than a sperm or egg

cell) is removed and the rest of the cell discarded. At

the same time, the nucleus of an egg cell is removed.

The nucleus of the somatic cell is then inserted intothe enucleated egg cell.

Somatic cell nuclear transfer (SCNT)


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Known asHuman embrionic stem cell (hESC)

President Bush : Human cloning 'morally wrong,November 26, 2001 limited federal tax dollars for embryonic stem cell

2009 approved by FDA

Current : Spine Injury Trial (GRNOPC1) by Geron Inc

Human stroke trial: Not yet

I d d Pl i t t St C ll (IPS)


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Induced Pluripotent Stem Cell (IPS)

Latest research in Stem Cells

claim to be the 'ultimate stem cell solution

Pluripotent stem cells artificially derived from a non-pluripotent cell, typically an adult somatic cells, byinducing a "forced" expression of certain genes.

IPSCs were first produced in 2006 from mouse cells andin 2007 from human cells

Because viruses are used to genomically alter the cells,the expression of cancer-causing genes or oncogensmay potentially be triggered

in April 2009, the group of Sheng Ding in La Jolla,California, could show that the generation of iPS cellswas possible without any genetic alteration of the adultcell via poly Arginine anchors call Protei n Induced

Pluripotent Stem Cell (pIPS)


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It was claim Save and stable

MATTERS ARISING iPS CELL SAFETY AND ETHICS,1,2

Human stroke Trial : Not yet establish


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HB1.F3 human NSC line

immortalized cell lines of human NSCs from primary human fetaltelencephalon cultures via a retroviral vector encoding v-myc. HB1.F3

Previously, a clonal human neural stem cell line (HB1.F3) that had beenimmortalized by a retroviral vector encoding the v-myc oncogene , andthisstable human cellline shows multipotent capacity to differentiate intoneurons and glial cells and ameliorate neurological deficits in animal modelsofstroke , Parkinsons disease , Huntingtons disease , and lysosomalstorage disease

Experimental ICH was induced in adult mice by intrastriatal administration

of bacterial collagenase; 1 week after surgery, the rats were randomlydivided into two groups so as to receive intracerebrally either humanNSCs labeled with galactosidase (n 31) or phosphate-buffered saline(PBS) (n 30).

Brain Transplantation of Immortalized Human Neural Stem Cells Promotes Functional Recovery in Mouse Intracerebral Hemorrhage StrokeModel, STEMCELLS 2007;25:12041212

Cell Transplantation for Intracerebral Hemorrhage


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In conclusion, F3 human NSC line can beinduced to differentiate into neurons and glialcells in vitro and in vivo and has a potential to

produce several neuroprotective factors,including NGF and BDNF.The present studydemonstrates that F3 human NSC cell line isnot only a useful tool for the studies of

neurogenesis but also as a renewable cellsource for the stem cell-based cell therapy inthe CNS diseases


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Cell Tracking and Imaging

MRI has been the mainstay for tracking implantedstem cells in vivo (7-14 T)

Superparamagnetic particles, such as iron oxide

nanoparticles, have been the most commonly usedcell-labeling substancesso far(SPIOs),(USPIOs),(MPIOS).

PET and SPECT with radiolabelling

MicroCT as a New Method for in vivo Cell Tracking

Max spatial res: Conventional: mCT :0.5 mm, 0.3 m


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Stem Cell Tracking by Nanotechnologies Int. J. Mol. Sci. 2010, 11, 1070-1081

Special Conditions in the Design of Clinical


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Special Conditions in the Design of Clinical

Stroke Trials for Cell Transplantation

ANATOMY

TIMING

VASCULATURE

SITE OF IMPLANT

PATIENTS

DELIVERY


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ADDITIONAL

Role of medicine: Statin 1,2, Valproic Acid

Role of Neurologist,1,2

Current Status in Indonesia

SUMMARY


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SUMMARY

Review : Restorative therapy in stroke using stem cells Neurology India | Jul-Aug 2009 | Vol 57 | Issue 4

www.stemcellthera.comREVIEW: BIOLOGICAL RESTORATION OF CENTRAL NERVOUS SYSTEM ARCHITECTURE AND FUNCTION: PART 3 STEM CELL AND CELL-BASED APPLICATIONS

AND REALITIES IN THE BIOLOGICAL MANAGEMENT OF CENTRAL NERVOUS SYSTEM DISORDERS:TRAUMATIC, VASCULAR, AND EPILEPSY DISORDERS,

Neurosurgery 65:831859, 2009


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