Stem Cells and Clinical Applications (2)
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Stem Cell BiologyStem Cell Biologyand Clinicaland Clinical
ApplicationsApplicationsDr.T.V.Rao MDDr.T.V.Rao MD
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Nerve Cell CannotNerve Cell CannotRegenerateRegenerate??
In 1913 the great SpanishIn 1913 the great Spanishneuroscientistneuroscientist Santiago Ramn ySantiago Ramn yCajalCajalpronounced that in adultpronounced that in adultcentres the nerve paths arecentres the nerve paths aresomething fixed, ended, immutable.something fixed, ended, immutable.Everything may die, nothing may beEverything may die, nothing may be
regenerated. For many yearsregenerated. For many yearsneuroscientists believed not just thatneuroscientists believed not just thatbrain damage was irreparable.brain damage was irreparable.
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antiago Ramn y Cajalantiago Ramn y Cajal(1852-1934)(1852-1934)
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Both beliefs turned out to be falseBoth beliefs turned out to be falseas several types of cells canas several types of cells can
regenerateregenerate
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Cell A complex OrganCell A complex Organ
Cell Theory: all livingCell Theory: all livingthings are composedthings are composedof one or more cellsof one or more cells
Cells fall into twoCells fall into two
basic typesbasic typesprokaryotic andprokaryotic andeukaryotic.eukaryotic.
Prokaryotic cells areProkaryotic cells aresmaller and lacksmaller and lackmuch of the internalmuch of the internalcompartmentalizincompartmentalizing and complexity ofg and complexity of
eukaryotic cellseukaryotic cells..
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Stem Cell DefinitionStem Cell Definition
A cell that hasA cell that hasthe ability tothe ability tocontinuouslycontinuouslydivide anddivide anddifferentiatedifferentiate(develop) into(develop) into
various othervarious otherkind ofkind ofcells/tissuescells/tissues
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On division, one daughter cellOn division, one daughter cellreplenishes a whole compartment, andreplenishes a whole compartment, and
the other remains fully stemthe other remains fully stem
.
.
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Stem CellsStem Cells
Stem cells are theStem cells are theraw material fromraw material fromwhich all of thewhich all of the
bodys mature,bodys mature,differentiated cellsdifferentiated cellsare made. Stemare made. Stemcells give rise tocells give rise to
brain cells, nervebrain cells, nervecells, heart cells,cells, heart cells,pancreatic cells, etc.pancreatic cells, etc.
S C ll
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Stem Cell aretem e areDynamicDynamic
AreAreundifferentiatedundifferentiatedmastermastercell thatcell thatdo not yet have ado not yet have a
specific functionspecific function Can change to oneCan change to one
or several differentor several differentcell typescell types
(differentiate)(differentiate)under properunder properconditionsconditions
Can undergoCan undergo
unlimited cellunlimited cell--
Stem cell
Stem cell
Self-renew
al
Specialized cell(e.g., white blood cell)
Differe
ntia
te
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One Cell - SeveralOne Cell - Severallineageslineages
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Generation of embryonicGeneration of embryonicstem cellsstem cells
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When does Stem CellsWhen does Stem Cellsarisearise
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The Science of Stem CellsThe Science of Stem Cells
Stem cells have the ability toStem cells have the ability to continuallycontinuallyreproduce themselvesreproduce themselves while maintainingwhile maintainingthe capacity to give rise to other morethe capacity to give rise to other morespecialized cells.specialized cells.
Stem cells are found at all stages ofStem cells are found at all stages ofdevelopment, from embryonic stem (ES)development, from embryonic stem (ES)cells that can differentiate into allcells that can differentiate into allspecialized cells found in the human body,specialized cells found in the human body,
to adult stem cells capable of regeneratingto adult stem cells capable of regeneratingtheir tissue of origin.their tissue of origin.
St em c el ls oc cur fr om the e ar l iestt em c el ls oc cur fr om t he e ar l iestst ages of dev el opm en t an d pr ovi de thet ages of dev el opm en t an d pr ovi de thest a rt ing m a te ri a l f o r ev er y or ga n an dt a rt i ng m a te ri a l f o r ev er y or ga n an d
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y uStem CellStem CellResearchResearch
Since the 1970s,Since the 1970s, bonebonemarrowmarrow transplants havetransplants havebeen used for treatment ofbeen used for treatment of
ImmunodeficientImmunodeficient andandleukemia.leukemia.
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Stem Cell HistoryStem Cell History
19981998 - Researchers first extract stem cells from human- Researchers first extract stem cells from humanembryosembryos
19991999 - First Successful human transplant of insulin-- First Successful human transplant of insulin-making cells from cadaversmaking cells from cadavers
20012001 - President Bush restricts federal funding for- President Bush restricts federal funding for
embryonic stem-cell researchembryonic stem-cell research 20022002 - Juvenile Diabetes Research Foundation- Juvenile Diabetes Research Foundation
International creates $20 million fund-raising effort toInternational creates $20 million fund-raising effort tosupport stem-cell researchsupport stem-cell research
2003??2003?? - California ok stem cell research- California ok stem cell research 20042004 - Harvard researchers grow stem cells from- Harvard researchers grow stem cells from
embryos using private fundingembryos using private funding 20042004 - Ballot measure for $3 Billion bond for stem cells- Ballot measure for $3 Billion bond for stem cells
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In 1998, James Thomson (University ofIn 1998, James Thomson (University ofWisconsin-Madison) isolated cells from theWisconsin-Madison) isolated cells from theinner cell mass of the early embryo, andinner cell mass of the early embryo, and
developed the first human embryonicdeveloped the first human embryonicstem cell lines,stem cell lines,
History of Human EmbryonicHistory of Human EmbryonicStem Cell ResearchStem Cell Research
In 1998, John Gearhart (Johns
Hopkins University) derivedhuman embryonic germ cellsfrom cells in fetal gonadal tissue(primordial germ cells).
Pluripotent stem cell lineswere develo ed from both
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Embryogenesis andEmbryogenesis andDifferentiationDifferentiation
Specific regions of the embryo give rise toSpecific regions of the embryo give rise tothe specific organ systemsthe specific organ systems EctodermEctoderm generates the outer layer ofgenerates the outer layer of
the embryo and produces the surfacethe embryo and produces the surface
layer (epidermis) of the skin and formslayer (epidermis) of the skin and formsthe nervesthe nerves EndodermEndoderm becomes the innermostbecomes the innermost
layer of the embryo and produces thelayer of the embryo and produces the
digestive tube and its associateddigestive tube and its associatedorgans (including the lungs)organs (including the lungs)
MesodermMesoderm becomes sandwichedbecomes sandwichedbetween the ectoderm and endodermbetween the ectoderm and endoderm
and generates the blood, heart, kidney,and generates the blood, heart, kidney,
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Stages of DevelopmentStages of Development
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An Overview of Early DevelopmentAn Overview of Early Development
modeled with Play-Doughmodeled with Play-DoughFertilized egg
Totipotent
stem cells
Totipotent: Can become any cell inbody or placenta
Fate Decision
Pluripotent
stem cells
(3-5 days old)
Blastocyst
Pluripotent: Can become any cell in
body
Implantation
Fate Decision
Gastrulating (day 14) leads to
Primary Germ Cells
Endoderm (inner) digestive tract, resp. track
Mesoderm (middle) bones, blood cells, heart
Ectoderm (outer) skin, CNS
Multipotent: Can become any cell
within a specific germ layer or celllineage
Embryonic stem cells come from inner cell mass of blastocyst.
Implantation
Fate Decision
Gastrulation (day 14) leads to
Primary Germ Cells
Endoderm (inner) digestive tract, resp. track
Mesoderm (middle) bones, blood cells, heart
Ectoderm (outer) skin, CNS
Multipotent: Can become any cell
within a specific germ layer or celllineage
Multipotent
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Other Cell typesOther Cell types
Oligopotent cell can form more than oneOligopotent cell can form more than onecell lineage, but more restricted thancell lineage, but more restricted thanmultipotent, also called as progenitor cellsmultipotent, also called as progenitor cells
or precursor cells.or precursor cells. Unipotent cells or monopotent egUnipotent cells or monopotent eg
spermatogonial stem cells can only form aspermatogonial stem cells can only form asingle differentiated cell lineage.single differentiated cell lineage.
Fibroblast cell capacity to proliferate butFibroblast cell capacity to proliferate butmaintain same cell type can not formmaintain same cell type can not formanother cell type.another cell type.
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Bone Marrow Stem CellsBone Marrow Stem Cells
How to Der ve an Em ryon cow o er ve an m ryon c
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How to Der ve an Em ryon cow o er ve an m ryon cStem Cell Line?Stem Cell Line?
Inner cell mass
Day 5-6Blastocyst
Isolate inner cell mass(destroys embryo)ETHICS?
Culture cells
A stem cell line is
composed of a
population of cellsthat can replicate
themselves for
long periods of
time in vitro
(out of the body) An embryonic
stem cellclone
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Embryonic stem (ES) cellsEmbryonic stem (ES) cells
ES cells areES cells arefound at thefound at theblastocystblastocyst
stage, four tostage, four tofive days afterfive days afterthe union of thethe union of thesperm and egg,sperm and egg,
before thebefore theembryoembryoimplants in theimplants in the
uterus.uterus.
ES C ll " l i t t" iES C ll " l i t t" i
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ES Cells are "pluripotent" - i.e.ES Cells are "pluripotent" - i.e.capable of forming embryoniccapable of forming embryonic
tissuestissues
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Source of Stem cellsSource of Stem cells
Stem cells may be derived fromStem cells may be derived fromautologus, allogeneic or xenogenicautologus, allogeneic or xenogenicsources.sources. Histocompatability isHistocompatability isprerequisite for transplantation ofprerequisite for transplantation ofallogeneic stemallogeneic stemcellscells. Fetal tissue is. Fetal tissue isthe best current tissue source forthe best current tissue source for
human neural stem cells, howeverhuman neural stem cells, howeverethical issues are a major concern.ethical issues are a major concern.
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Placenta a Source of StemPlacenta a Source of StemCellsCells
Placental stemPlacental stemcells, like umbilicalcells, like umbilicalcord blood andcord blood and
bone marrow stembone marrow stemcells, can be usedcells, can be usedto cure chronicto cure chronicblood-relatedblood-related
disorders such asdisorders such assickle cell disease,sickle cell disease,
Thalasemia, andThalasemia, andleukaemia.leukaemia.
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P acenta B oo as a ource oacen a oo as a ource o
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Report ofReport ofpreliminary resultspreliminary results
of transplantationof transplantationusing partially HLA-using partially HLA-mismatchedmismatchedplacental bloodplacental bloodfrom unrelatedfrom unrelateddonors.donors.Joanne Kurtzberg,Joanne Kurtzberg,M.D.et alM.D.et al
P acenta B oo as a ource oacen a oo as a ource oHematopoietic Stem Cells forHematopoietic Stem Cells for
Transplantation into UnrelatedTransplantation into Unrelated
RecipientsRecipients
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Umbilical Cord Blood StemUmbilical Cord Blood StemCell TransplantCell Transplant
Umbilical cord bloodUmbilical cord bloodstem cell transplantsstem cell transplantsare less prone toare less prone torejection than eitherrejection than either
bone marrow orbone marrow orperipheral blood stemperipheral blood stemcells. This is probablycells. This is probablybecause the cells havebecause the cells have
not yet developed thenot yet developed thefeatures that can befeatures that can berecognized andrecognized andattacked by theattacked by therecipient's immunerecipient's immunesystemsystem
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Whats So Special AboutWhats So Special AboutStem Cells?Stem Cells?
They have the potential toThey have the potential to replace cellreplace celltissuetissue that has been damaged orthat has been damaged ordestroyed by severe illnesses.destroyed by severe illnesses.
They can replicate themselves over andThey can replicate themselves over andover for a very long time.over for a very long time.
Understanding how stem cells developUnderstanding how stem cells developinto healthy and diseased cells willinto healthy and diseased cells willassist the search for cures.assist the search for cures.
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Two Kinds of StemTwo Kinds of Stem
CellsCells
EmbryonicEmbryonic (also called(also calledpluripotent)pluripotent) stem cells arestem cells are
capable of developing into all thecapable of developing into all thecell types of the body.cell types of the body.
Adult stem cells are lessAdult stem cells are lessversatile and more difficult toversatile and more difficult toidentify, isolate, and purify.identify, isolate, and purify.
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Stages of EmbryogenesisStages of Embryogenesis
Day 1Fertilized egg
Day 22-cell embryo Day 3-4Multi-cell embryo
Day 5-6BlastocystDay 11-14
Tissue Differentiation
Derivation and Use ofer vat on an se o
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Derivation and Use ofer vat on an se oEmbryonic Stem CellEmbryonic Stem Cell
LinesLinesIsolate inner cell mass(destroys embryo)
Heart muscleKidney
Liver
Special sauce(largely unknown)
Day 5-6Blastocyst
Inner cells
(forms fetus)
Outer cells(forms placenta)
Heart
repaired
Culture cells
w y u
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w y uEmbryonic Stem CellEmbryonic Stem Cell
Lines are ThereLines are There??The actual number of humanThe actual number of humanembryonic stem cell lines is a matterembryonic stem cell lines is a matterof some debate.of some debate.
To date,To date, more than 100more than 100 humanhumanembryonic stem cell lines have beenembryonic stem cell lines have beenderived worldwide.derived worldwide.
However, most of those lines are notHowever, most of those lines are notadequately characterized yet.adequately characterized yet.
Only 22 cell lines are eligible forOnly 22 cell lines are eligible forfederal fundin in the
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Autologous Stem CellsAutologous Stem Cells
Sources of theSources of thepatient's own stempatient's own stemcells (autologous)cells (autologous)are either the cellsare either the cells
from patient's ownfrom patient's ownbody or his or herbody or his or hercord blood. Forcord blood. Forautologousautologoustransplantstransplants
physicians nowphysicians nowusually collect stemusually collect stemcells from thecells from theperipheral bloodperipheral bloodrather than therather than the
marrowmarrow
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Allogeneic Stem CellsAllogeneic Stem Cells
Sources of stem cellsSources of stem cellsfrom another donorfrom another donor(allogeneic) are(allogeneic) areprimarily relativesprimarily relatives
(familial-allogeneic) or(familial-allogeneic) orcompletely unrelatedcompletely unrelateddonors (unrelated-donors (unrelated-allogeneic). The stemallogeneic). The stem
cells in this situationcells in this situationare extracted fromare extracted fromeither the donor's bodyeither the donor's bodyor cord bloodor cord blood
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Xenogenic - Stem CellsXenogenic - Stem Cells In this stem cells fromIn this stem cells from
different species aredifferent species aretransplanted, e.g.transplanted, e.g.striatal porcine fetalstriatal porcine fetalventral mesencephalicventral mesencephalic
(FVM) xenotransplants(FVM) xenotransplantsfor Parkinson'sfor Parkinson'sdisease. This has nodisease. This has nomajor ethical concernsmajor ethical concernsand a large amount ofand a large amount oftissue is available,tissue is available,however life longhowever life longimmunosupression andimmunosupression andrisk of rejection are therisk of rejection are themajor limitationsmajor limitations
How Does Cell TherapyHow Does Cell Therapy
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How Does Cell TherapyHow Does Cell TherapyWork?Work?
Stem cells can beStem cells can beused to generateused to generatehealthy andhealthy andfunctioningfunctioning
specialized cells,specialized cells,which can thenwhich can thenreplace diseasedreplace diseasedor dysfunctionalor dysfunctional
cells.cells. It is similar to theIt is similar to the
process of organprocess of organtransplantation onlytransplantation only
the treatmentthe treatmentconsists ofconsists of
ow oes eow oes e
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ow oes eow oes eTherapy Work?Therapy Work?
Bone marrow transplantsBone marrow transplants are anare anexample of cell therapy in which theexample of cell therapy in which thestem cells in a donor's marrow are usedstem cells in a donor's marrow are usedto replace the blood cells of the victimsto replace the blood cells of the victims
of leukemia.of leukemia. Cell therapy is also being used inCell therapy is also being used inexperiments toexperiments to graft new skingraft new skincellscells tototreat serious burn victims, and totreat serious burn victims, and to growgrow
new corneasnew corneas for the sight-impaired.for the sight-impaired. In all of these uses, the goal is forIn all of these uses, the goal is for
the healthy cells to becomethe healthy cells to become
integrated into the body and beginintegrated into the body and beginto function like the atient's ownto function like the atient's own
What Diseases Can beWhat Diseases Can be
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What Diseases Can beWhat Diseases Can beCured by Stem CellCured by Stem Cell
TherapiesTherapies Any diseaseAny diseasein whichin which
there isthere istissuetissuedegenerationdegeneration
can be acan be apotentialpotentialcandidate forcandidate for
stem cellstem cell
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Major Progress in SeveralMajor Progress in SeveralImportant Health problemsImportant Health problems
AlzheimersAlzheimersdiseasedisease
ParkinsonsParkinsons
diseasedisease Spinal cord injurySpinal cord injury Heart diseaseHeart disease
Severe burnsSevere burns DiabetesDiabetes
Alzheimers disease andAlzheimers disease and
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Alzheimer s disease andAlzheimer s disease andcan stem cells help?can stem cells help?
Stem cells could,Stem cells could,however, behowever, begenetically modifiedgenetically modifiedso as to deliverso as to deliversubstances to thesubstances to theAlzheimer brain, toAlzheimer brain, tostop cells from dyingstop cells from dyingand stimulate theand stimulate thefunction of existingfunction of existingcells. A recent clinicalcells. A recent clinicaltrial (Phase I) hastrial (Phase I) has
shown this approachshown this approachto be of some benefitto be of some benefitto patients withto patients withAlzheimers disease,Alzheimers disease,by slowing down theby slowing down theprogression of theprogression of thedisease.disease.
i
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Drug TestingDrug Testing
Stem cells could allowStem cells could allowscientists to test new drugsscientists to test new drugsusing human cell line whichusing human cell line which
could speed up new drugcould speed up new drugdevelopment.development.Only drugs that were safeOnly drugs that were safe
and had beneficial effects inand had beneficial effects in
cell line testing wouldcell line testing wouldgraduate to whole animal orgraduate to whole animal orhuman testing.human testing.
It would allow quicker andIt would allow quicker and
S ll
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Stem cells act asStem cells act asProgenitor cellsProgenitor cells
In adult organisms,In adult organisms,stem cells andstem cells andprogenitor cellsprogenitor cells
act as a repairact as a repairsystem for thesystem for thebody, replenishingbody, replenishingspecialized cells,specialized cells,
but also maintainbut also maintainthe normalthe normalturnover ofturnover ofregenerativeregenerative
organs, such asorgans, such as
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s ory o n mas ory o n ma
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s ory o n mas ory o n maCloningCloning
Since then, animals including mice(1998), cows (1998), pigs (2000), cats(2001), and rabbits (2002) weresuccessfully cloned.
RABBIT
MOUSE
CAT
Cattle
PIG
w u u
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Dolly(sheep)
1 live birth out of 29 clonedembryos
3%
Cloned mice 31 live births out of 2468cloned embryos
1%
Cloned pigs 5 live births out of 335cloned embryos 1%
Cloned goats 3 live births out of 85 clonedembryos
3%
Clonedcattle
30 live births out of 496cloned embryos 6%
Cloned cat 1 live birth out of 87 clonedembryos
1%
Clonedrabbits
6 live births out of 371 of
cloned embryos
1%
w u uAnimal Cloning? VeryAnimal Cloning? Very
low (~1-3%)low (~1-3%)
First Success of HumanFirst Success of Human
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First Success of HumanFirst Success of HumanEmbryo CloningEmbryo Cloning
On February 12, 2004, SouthKorean scientists, Dr. Woo SukHwang and Dr. Shin Young Moonof Seoul National University,reported the successful creation
of30 cloned human embryosdeveloped to the blastocyststage and then destroyed by
stem cell extraction yielding
S f St C ll fS f St C ll f
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Source of Stem Cells forSource of Stem Cells forMedical therapiesMedical therapies
Tens of thousands ofTens of thousands offrozen embryos arefrozen embryos areroutinely destroyedroutinely destroyedwhen couples finishwhen couples finish
their treatment.their treatment. These surplusThese surplus
embryos can beembryos can beused to produceused to produce
stem cells.stem cells. RegenerativeRegenerative
medical researchmedical researchaims to developaims to develop
these cells into new,these cells into new,
tem e Researcem e esearc
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tem e Researcem e esearcWorldwideWorldwide
Adult Mutipotent StemAdult Mutipotent Stem
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Adult Mutipotent StemAdult Mutipotent StemCellsCells
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Adult Stem Cells
HumanHuman embryonicembryonic stem cellsstem cells
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yyA: Cell colonies that are not yet differentiated.A: Cell colonies that are not yet differentiated.
B:B: NerveNerve cellcell
http://en.wikipedia.org/wiki/Embryohttp://en.wikipedia.org/wiki/Embryohttp://en.wikipedia.org/wiki/Nervehttp://en.wikipedia.org/wiki/Embryo -
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Autologus Stem CellsAutologus Stem Cells
While most blood stemWhile most blood stemcells reside in the bonecells reside in the bonemarrow, a smallmarrow, a smallnumber are present innumber are present in
the bloodstream.the bloodstream.These multipotentThese multipotentperipheral blood stemperipheral blood stemcells, or PBSCs, can becells, or PBSCs, can be
used just like boneused just like bonemarrow stem cells tomarrow stem cells totreat leukaemia, othertreat leukaemia, othercancers and variouscancers and variousblood disordersblood disorders
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Stem Cell ReplacementsStem Cell Replacements
1. Injection of stem cells directly into the1. Injection of stem cells directly into thedamaged tissue.damaged tissue.
2.In vitro differentiation of stem cell followed2.In vitro differentiation of stem cell followedby transplantation into the damaged organ,by transplantation into the damaged organ,eg pancreas islet cells could be generatedeg pancreas islet cells could be generatedfrom the stem cells prior to transplantationfrom the stem cells prior to transplantation
into patients with diabetes, cardiomyocytesinto patients with diabetes, cardiomyocytescould be generated to treat ischemic heartcould be generated to treat ischemic heartdisease.disease.
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Stem Cell ReplacementsStem Cell Replacements
3. Stimulation of endogenous stem3. Stimulation of endogenous stemcells to facilitate repair eg,cells to facilitate repair eg,
administration of appropriate growthadministration of appropriate growthfactors to amplify numbers offactors to amplify numbers ofendogenous stem cell/ progenitor cellsendogenous stem cell/ progenitor cellsor direct them to differentiate intoor direct them to differentiate intodesired cell typesdesired cell types
Stem cells are also excellentStem cells are also excellentvehicles for cellular gene therapyvehicles for cellular gene therapy..
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Stem cell InfusionStem cell Infusion
S l ti
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multipoten
t
Speculation
ow oes eow oes e
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ow oes eow oes eTherapy Work?Therapy Work?
Stem cells can be used to generateStem cells can be used to generatehealthy and functioning specializedhealthy and functioning specializedcells, which can then replace diseasedcells, which can then replace diseasedor dysfunctional cells.or dysfunctional cells.
It is similar to the process of organIt is similar to the process of organtransplantation only the treatmenttransplantation only the treatmentconsists ofconsists oftransplanting cellstransplanting cellsinstead of organsinstead of organs..
Day 5-6
Blastocyst Heart
tissues
Nerve
tissues
Bone
tissues
Special sauce
(largely unknown)
ow oes eow oes e
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ow oes eow oes eTherapy WorkTherapy Work??
Bone marrow transplantsBone marrow transplants are anare anexample of cell therapy in which theexample of cell therapy in which thestem cells in a donor's marrow are usedstem cells in a donor's marrow are usedto replace the blood cells of the victimsto replace the blood cells of the victims
of leukemia.of leukemia.
Cell therapy is also being used inCell therapy is also being used inexperiments toexperiments to graft new skingraft new skincellscells tototreat serious burn victims, and totreat serious burn victims, and to growgrow
new corneasnew corneas for the sight-impaired.for the sight-impaired. In all of these uses, the goal is forIn all of these uses, the goal is for
the healthy cells to becomethe healthy cells to becomeintegrated into the body and beginintegrated into the body and beginto function like the atient's ownto function like the atient's own
Treatments becomesTreatments becomes
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Treatments becomesTreatments becomesSpecificSpecific
d b ll
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Cured by Stem CellCured by Stem Cell
Therapies?Therapies?Any disease in which there is tissueAny disease in which there is tissuedegeneration can be a potentialdegeneration can be a potentialcandidate for stem cell therapiescandidate for stem cell therapies
Alzheimers diseaseParkinsons disease
Spinal cord injuryHeart diseaseSevere burns
Diabetes
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Sources of Stem CellsSources of Stem Cells
EmbryonicEmbryonic
Adult TissuesAdult Tissues Adipose tissue (adipose stem cell, ASC)Adipose tissue (adipose stem cell, ASC) Bone marrow (hematopoietic stem cell, HSC)Bone marrow (hematopoietic stem cell, HSC) Bone marrow (mesenchymal stem cell, MSC)Bone marrow (mesenchymal stem cell, MSC)
Liver (hepatic stem cell)Liver (hepatic stem cell) Nervous tissue (neural stem cell, NSC)Nervous tissue (neural stem cell, NSC) PancreasPancreas
w y uE b i S C ll
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w y uEmbryonic Stem CellEmbryonic Stem Cell
Lines are There?Lines are There?The actual number of humanThe actual number of humanembryonic stem cell lines is aembryonic stem cell lines is amatter of some debate.matter of some debate.
To date,To date, more than 100more than 100 humanhumanembryonic stem cell lines haveembryonic stem cell lines havebeen derived worldwide.been derived worldwide.
However, most of those lines areHowever, most of those lines arenot adequately characterized yet.not adequately characterized yet.Only 22 cell lines are eligible forOnly 22 cell lines are eligible for
federal funding in thefederal funding in theUSA USA
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Applications of Stem CellsApplications of Stem Cells
Cell Replacement TherapiesCell Replacement Therapies Cells could be stimulated to develop intoCells could be stimulated to develop into
specialized cells that representspecialized cells that representrenewable sources of cells and tissue forrenewable sources of cells and tissue fortransplantation.transplantation.
Cell replacement therapy could treatCell replacement therapy could treatinjuries and various genetic andinjuries and various genetic anddegenerative conditions includingdegenerative conditions includingmuscular dystrophies, retinalmuscular dystrophies, retinaldegeneration, Alzheimer disease,degeneration, Alzheimer disease,Parkinson's disease, arthritis, diabetes,Parkinson's disease, arthritis, diabetes,spinal cord injuries, and blood disordersspinal cord injuries, and blood disorderssuch as hemophilia.such as hemophilia.
Understanding CellUnderstanding Cell
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Understanding CellUnderstanding CellSpecializationSpecialization
Studying human pluripotent stem cells canStudying human pluripotent stem cells can
lead to the identification of factors responsiblelead to the identification of factors responsiblefor differentiation of stem cells into specializedfor differentiation of stem cells into specialized
cell types.cell types. these factors may ultimately be used to drive tissuethese factors may ultimately be used to drive tissue
regeneration and repair if administeredregeneration and repair if administeredtherapeutically.therapeutically.
This work will provide basic knowledge on cellThis work will provide basic knowledge on celldetermination and differentiation, humandetermination and differentiation, humandevelopment, genomic imprinting and somaticdevelopment, genomic imprinting and somaticcell aging.cell aging.
Development and TestingDevelopment and Testing
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Development and TestingDevelopment and Testingof Drugsof Drugs
ResearchersResearchers
could study thecould study thebeneficial andbeneficial and
toxic effects oftoxic effects ofnewnewmedications onmedications onhumanhuman
pluripotent stempluripotent stemcells that havecells that havebeen developedbeen developedto mimic theto mimic the
diseasedisease
Can Sex Make difference inCan Sex Make difference in
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Can Sex Make difference inCan Sex Make difference inStem cell Therapy ?Stem cell Therapy ?
Are there sex-specificAre there sex-specificdifferences in thedifferences in thebiology of stem cells?biology of stem cells?(short-long term(short-long term
How do sex-specificHow do sex-specific
differences play out indifferences play out interms of self-renewalterms of self-renewaland differentiation?and differentiation?(mid-long term)(mid-long term)
Is there existingIs there existing
evidence that the sexevidence that the sexof stem cells affectsof stem cells affectssuccess of thesuccess of thetransplant?transplant?
XXXX vs.vs.
XXYY
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L V Prasad Eye InstituteL V Prasad Eye Institute
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L V Prasad Eye Institute,L V Prasad Eye Institute,HyderabadHyderabad
Bone Marrow Stem Cells MayBone Marrow Stem Cells Mayi
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yyCure Eye DiseaseCure Eye Disease
Bone marrow stemBone marrow stemcells can switchcells can switchroles and produceroles and producekeratocankeratocan, a natural, a naturalprotein involved inprotein involved in
the growth of thethe growth of thecorneacorneathethetransparent, outertransparent, outerlayer of the eyeball.layer of the eyeball.This ability ofThis ability of
marrow cells tomarrow cells todifferentiate intodifferentiate intokeratocan-keratocan-producing cellsproducing cellsmight provide amight provide a
means for treatingmeans for treating
i b l ll hLi b l t C ll th
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Limbal stem Cell therapyLimbal stem Cell therapy
The treatment isThe treatment isknown as limbal stemknown as limbal stemcell therapy, and thecell therapy, and thepatients who receivedpatients who receivedthe treatment sufferedthe treatment sufferedfrom chemical burn orfrom chemical burn orgenetic disease knowgenetic disease knowas aniridiaas aniridia
By replacing theBy replacing the
limbal stem cells, thelimbal stem cells, thecornea begins to clearcornea begins to clearup as the cells areup as the cells arereplaced with thereplaced with thehealthy transparenthealthy transparent
layer again.layer again.
LV P d E I iLV P d E I tit t
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LV Prasad Eye InstituteLV Prasad Eye Institute
Research begun byResearch begun byLV Prasad scientists,LV Prasad scientists,who use eye stemwho use eye stemcells from livingcells from livingadults to grow newadults to grow newcells that are thencells that are thenimplanted intoimplanted intodamaged eyes.damaged eyes.
The centre's goal isThe centre's goal is
to restore vision toto restore vision tosome portion of thesome portion of the65 million people65 million peopleworldwideabout 1worldwideabout 1percent of the worldpercent of the worldpopulationconsideredpopulationconsidered
to be legally blind,to be legally blind,
C iblC t ibl
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Current possible usesCurrent possible uses
Research in stem cells has opened upResearch in stem cells has opened upnew horizons in the area of treatmentnew horizons in the area of treatmentof disorders such as stroke, epilepsy,of disorders such as stroke, epilepsy,
neuro-degeneration and trauma.neuro-degeneration and trauma.Current research is aimed at findingCurrent research is aimed at findingthe appropriate source of stem cellsthe appropriate source of stem cellsfor a given indication, ways offor a given indication, ways of
expanding and perpetuating theseexpanding and perpetuating thesecells in culture, best route ofcells in culture, best route ofadministration of these cells andadministration of these cells andmethods to overcome rejectionmethods to overcome rejection
Unknowns in Stem Cell/CloningUnknowns in Stem Cell/Cloning
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Unknowns in Stem Cell/CloningUnknowns in Stem Cell/CloningResearchResearch
It is uncertain that human embryonicIt is uncertain that human embryonicstem cellsstem cells in vitroin vitro can give rise to allcan give rise to allthe different cell types of the adultthe different cell types of the adult
body.body. It is unknown if stem cells culturedIt is unknown if stem cells cultured inin
vitrovitro (apart from the embryo) will(apart from the embryo) will
function as the cells do when they arefunction as the cells do when they arepart of the developing embryopart of the developing embryo
Obstacles of Stem CellObstacles of Stem Cell
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ResearchResearch
How to find the right type of stemHow to find the right type of stemcells?cells?
How to put the stem cells into theHow to put the stem cells into the
right place?right place?Will the stem cells perform theWill the stem cells perform thedesired function in the body?desired function in the body?
Differentiation protocols for manyDifferentiation protocols for manycell types have not beencell types have not beendeveloped.developed.
Possible Uses of Stem CellPossible Uses of Stem Cell
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Possible Uses of Stem CellPossible Uses of Stem CellTechnologyTechnology
ReplaceableReplaceabletissues/organstissues/organs
Repair of defectiveRepair of defective
cell typescell types Delivery of geneticDelivery of genetic
therapiestherapies DeliveryDelivery
chemotherapeuticchemotherapeuticagentsagents
Future Making cells andFuture Making cells andl i h di d ll
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replacing the diseased cellsreplacing the diseased cells
??
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S i id G C ttS i id G C tt
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Suicide Gene CassetteSuicide Gene Cassette
All protocols usingAll protocols usingintegrating vectorsintegrating vectorsin hematopoieticin hematopoieticcells must include acells must include a
plan for monitoringplan for monitoringsites of insertionsites of insertionand Clonaland Clonalproliferation.proliferation.
Overcome byOvercome byincluding suicideincluding suicidegene cassette ingene cassette inthe vector.the vector.
New knowledge 0nNew knowledge 0n
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New knowledge 0ngEmbryonic Stem CellsEmbryonic Stem Cells
Recent advances include theRecent advances include theidentification of genes involved inidentification of genes involved inregulation of stem cell functionregulation of stem cell function
Prominent genes knownProminent genes known
Pou5f1, Nanog, andPou5f1, Nanog, and
Sox2Sox2govern the self renewal andgovern the self renewal andmaintenance of ES cell.maintenance of ES cell.
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La w int erf er es ina w int erf er es inSt em Ce llt em Ce llTh er apyh er apy
Bibli l A t SBiblical Arguments Summary
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Biblical Arguments: SummaryBiblical Arguments: Summary
The Bible indicates that GodThe Bible indicates that Godrecognizes human beings as personsrecognizes human beings as personsprior to development in the wombprior to development in the womb
Bible defines murder as beingBible defines murder as beingintentional and premeditatedintentional and premeditated
ESC research destroys embryos thatESC research destroys embryos that
are considered as ensouled humanare considered as ensouled humanbeingsbeings
Ethical debateEthical debate
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Ethical debateEthical debate
Harvesting ES cellsHarvesting ES cellsdestroys thedestroys theblastocystblastocyst
This is murderThis is murder ES cell researchES cell research
requires humanrequires humancellscells
Could create aCould create acommercialcommercialmarket for humanmarket for humancellscells
This devaluesThis devalues
ReproducedbypermissionofDaveCatrowandCopleyNews
Service
Destroying life to cureDestroying life to cure
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some one Ethicalsome one Ethical?? If stem cells have such potential toIf stem cells have such potential to
relieve suffering, why are so manyrelieve suffering, why are so manypeople so upset about their use? Thepeople so upset about their use? The
reason is that the most powerful typereason is that the most powerful typeof stem cell embryonic stem (ES)of stem cell embryonic stem (ES)cells can only be obtained fromcells can only be obtained from
human embryos. Many people thinkhuman embryos. Many people thinkthat it's wrong to create and destroythat it's wrong to create and destroyhuman embryos to treat diseasehuman embryos to treat disease
e g ous e a e overu vHarvestingHarvesting
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HarvestingHarvestingEmbryonic Stem CellsEmbryonic Stem Cells
The pro-life groupThe pro-life groupgenerally believesgenerally believesthat:that:
Personhood happensPersonhood happensat, or shortly after,at, or shortly after,conceptionconception..
Thus, they consider theThus, they consider the
removal of stem cellsremoval of stem cellsfrom an embryo -- afrom an embryo -- aprocedure which killsprocedure which killsthe stem cells -- to be athe stem cells -- to be a
form ofform of murder of amurder of a
Day 5-6
Blastocyst
e g ous e a e overu vHarvestingHarvesting
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HarvestingHarvestingEmbryonic Stem CellsEmbryonic Stem Cells
The pro-choice group generallyThe pro-choice group generallybelieves that:believes that:
Personhood is attainedPersonhood is attainedmuch later in pregnancy,much later in pregnancy,perhaps when the fetalperhaps when the fetal
brain developsbrain developsconsciousness during theconsciousness during thethird trimester.third trimester.
Thus, extracting stemThus, extracting stemcells from ancells from an five or ten-five or ten-
day old pre-embryo isday old pre-embryo isnot murdernot murder.. Killing a pre-embryo,Killing a pre-embryo,
which is only a potentialwhich is only a potentialhuman being, is justifiedhuman being, is justifiedif it has the potential toif it has the potential tocure diseases and extendcure diseases and extend
Day 5-6
Blastocyst
The Korean group established a cellThe Korean group established a cell
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line Cloned Human ESC Differentiateline Cloned Human ESC DifferentiateInto Different Tissue TypesInto Different Tissue Types AnAn
Academic FraudAcademic FraudNeural Retinal
Bone Cartilage Epithelial
Legal Considerations:Legal Considerations:
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ggEmbryonic Cell ResearchEmbryonic Cell Research
1973 moratorium on government1973 moratorium on governmentfinancing for human embryo researchfinancing for human embryo research
1988 NIH Panel voted 19-2 in favor of1988 NIH Panel voted 19-2 in favor of
government fundinggovernment funding1989 DHHS Secretary Sullivan1989 DHHS Secretary Sullivan
extended the moratoriumextended the moratorium
Legal Considerations:Legal Considerations:
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ggEmbryonic Cell ResearchEmbryonic Cell Research
1990 Congress voted to override the1990 Congress voted to override themoratorium, vetoed by President Bushmoratorium, vetoed by President Bush
1993 President Clinton lifted the ban1993 President Clinton lifted the ban
1994 the Human Embryo
Research Panel favoredresearch, but Clinton overrodethe panel
1995 Congress banned
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Why we should supportWhy we should support
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y ppy ppCan help several disabledCan help several disabled
HumanHumanembryonic stemembryonic stemcell (HESC)cell (HESC)
research offersresearch offersgreat promise ofgreat promise ofcures forcures for
otherwiseotherwiseincurableincurableconditions:conditions:spinal cordspinal cord
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Goal of Stem CellGoal of Stem Cell
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TherapiesTherapies
The goal of stem cellThe goal of stem cell
therapies is to promote celltherapies is to promote cellreplacement in organs thatreplacement in organs thatare damaged beyond theirare damaged beyond their
ability for self repairability for self repair
Tissue Engineering A newTissue Engineering A new
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branch in Medicinebranch in Medicine
The approach to tissue engineering containThe approach to tissue engineering containthe combination of three dimensionalthe combination of three dimensionalscaffold with live and functional cells.scaffold with live and functional cells.
Stem cells proving the ideal tool as they areStem cells proving the ideal tool as they are
capable of rapid proliferation and they cancapable of rapid proliferation and they canbe induced to differentiate into multiplebe induced to differentiate into multiplelineagelineage
Human embryonic are capable ofHuman embryonic are capable ofdifferentiation to endoderm, mesoderm, ordifferentiation to endoderm, mesoderm, or
ectoderm tissue typesectoderm tissue types Adult stem cells generate a relatively mutedAdult stem cells generate a relatively muted
immune responseimmune response..
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ConclusionsConclusions
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ConclusionsConclusions There is enormous potential in human stemThere is enormous potential in human stem
cell researchcell research
Both adult and embryonic stem cells shouldBoth adult and embryonic stem cells shouldbe studiedbe studied
Much research needed before therapies areMuch research needed before therapies arerealizedrealized Ethical concerns need to be taken intoEthical concerns need to be taken into
accountaccount Current guidelines are not adequateCurrent guidelines are not adequate Additional guidelines are needed to ensureAdditional guidelines are needed to ensure
appropriate conduct of the researchappropriate conduct of the research Adequate protection of donors fromAdequate protection of donors from
exploitation Sensible precautions against ill-exploitation Sensible precautions against ill-
consideredconsidered experimentsexperiments
Research on Stem Cells isResearch on Stem Cells isprogressing in spite of severalprogressing in spite of several
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progressing in spite of severalprogressing in spite of severalrestrictionsrestrictions
Australian Quadriplegic ThanksAustralian Quadriplegic ThanksMaverick Indian Stem Cell DoctorMaverick Indian Stem Cell Doctor
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Maverick Indian Stem Cell DoctorMaverick Indian Stem Cell Doctorfor Ability to Breathfor Ability to Breath
Perry Cross is thePerry Cross is themost high-profilemost high-profilepatient to havepatient to havetravelled to India totravelled to India tobe injected with thebe injected with thecells - which arecells - which arebanned in his ownbanned in his own
country Australiacountry Australiaand most of theand most of theWestWest
CryopreservationCryopreservation
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CryopreservationCryopreservation
CryopreservationCryopreservation is ais aprocess where cells orprocess where cells orwhole tissues arewhole tissues arepreserved by cooling topreserved by cooling tolow sub-zerolow sub-zero
temperatures, such astemperatures, such as(typically) 77 K or 196(typically) 77 K or 196C (the boiling point ofC (the boiling point ofliquid nitrogen). Atliquid nitrogen). Atthese lowthese lowtemperatures, anytemperatures, any
biological activity,biological activity,including theincluding thebiochemical reactionsbiochemical reactionsthat would lead to cellthat would lead to celldeath, is effectivelydeath, is effectively
stoppedstopped
CryoBanks IndiaCryoBanks India
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CryoBanks has 80CryoBanks has 80counselling centrescounselling centresacross the countyacross the countymanned by bio-techmanned by bio-techgraduates, who visitgraduates, who visithouseholds andhouseholds andhospitals to createhospitals to create
awareness andawareness andmarket the concept.market the concept.
CryoBanks IndiaCryoBanks India
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CryoBanks IndiaCryoBanks India
India is the seventhIndia is the seventhlargest and secondlargest and secondmost populousmost populouscountry in the worldcountry in the worldwith approximatelywith approximately20 million births per20 million births peryear representingyear representing
one of the largestone of the largestbirth markets in thebirth markets in theworld.world.
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ThankQ
Created for AwarenessCreated for Awareness
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Created for AwarenessCreated for Awareness
to Medical andto Medical andParamedical Students inParamedical Students in
Developing WorldDeveloping WorldDr.T.V.Rao MDDr.T.V.Rao MD
EmailEmail
[email protected]@gmail.com