Stem Cells and Progress of Science

8/4/2019 Stem Cells and Progress of Science

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Dr.T.V.Rao MD

STEM CELLSADVANCES IN SCIENCE

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STEM CELL DEFINITION

A cell that has the

ability to

continuously divideand differentiate

(develop) into

various otherkind(s) of

cells/tissues

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DR.T.V.RAO MD

WHAT MAKES A CELL A STEM CELL?

Plasticity: A stem cell is plastic, meaning it candevelop into another type of cell.

Differentiation: The process where a stem cellspecializes or develops into another type ofcell.

Self-Renewal: a stem cell can divide (renewitself) indefinitely(go through mitosis) andwithout always developing into another cell.

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STEM CELL HISTORY

1998 - Researchers first extract stem cells from human embryos

1999 - First Successful human transplant of insulin-making cellsfrom cadavers

2001 - President Bush restricts federal funding for embryonic stem-cell research

2002 - Juvenile Diabetes Research Foundation International creates$20 million fund-raising effort to support stem-cell research

2003?? - California ok stem cell research

2004 - Harvard researchers grow stem cells from embryos usingprivate funding

2004 - Ballot measure for $3 Billion bond for stem cells

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HISTORY OF HUMAN EMBRYONICSTEM CELL RESEARCH

In 1998, James Thomson(University ofWisconsin-Madison) isolated cells from the innercell mass of the blastocyst, and developed the first

human embryonic stem cell line in culture.

Isolate inner cell mass

Culture cells

Inner cell mass(forms fetus)

Day 5-6Blastocyst

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IN 1998, JAMES THOMSON (UNIVERSITY OF

WISCONSIN-MADISON) ISOLATED CELLS FROM

THE INNER CELL MASS OF THE EARLY EMBRYO,

AND DEVELOPED THE FIRST HUMAN EMBRYONICSTEM CELL LINES,

HISTORY OF HUMAN EMBRYONIC STEM CELLRESEARCH

In 1998, John Gearhart (JohnsHopkins University) derived human

embryonic germ cells from cells infetal gonadal tissue (primordialgerm cells).

Pluripotent stem cell lines were

developed from both sourcesDR.T.V.RAO MD 6


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WHAT ARE STEM CELLS?

Stem cells are the raw

material from which all of

the bodys mature,

differentiated cells aremade. Stem cells give

rise to brain cells, nerve

cells, heart cells,pancreatic cells, etc.

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DR.T.V.RAO MD

MAJOR TYPES OF STEM CELLS

Embryonic Stem Cells

Totipotent : cell can

develop into all celltypes

Immortal: can self-renew indefinitely

Plentiful

Adult Stem Cells

Multipotent: cell can develop

into a few cell types but notall

Located in few organs or

may be unidentified

Hard to find

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STEM CELL ARE DYNAMIC

Are undifferentiatedmastercell that do notyet have a specificfunction

Can change to one orseveral different cell types(differentiate) under properconditions

Can undergo unlimited celldivision, self-renewal)

Stem cell

Stem cell Specialized cell(e.g., white blood cell)

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ONE CELL - SEVERAL LINEAGES

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EMBRYOGENESIS ANDDIFFERENTIATION

Specific regions of the embryo giverise to the specific organ systems Ectodermgenerates the outer layer of the embryo

and produces the surface layer (epidermis) of the skinand forms the nerves

Endoderm becomes the innermost layer of the

embryo and produces the digestive tube and itsassociated organs (including the lungs)

Mesodermbecomes sandwiched between theectoderm and endoderm and generates the blood,

heart, kidney, gonads, bones, and connective tissues.DR.T.V.RAO MD 11


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STAGES OF DEVELOPMENT

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EARLY HUMAN DEVELOPMENT

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AN OVERVIEW OF EARLY DEVELOPMENT

MODELED WITH PLAY-DOUGH

Fertilized egg

Totipotentstem cells

Totipotent: Can become any cell inbody or placenta

Fate Decision

Pluripotentstem cells(3-5 days old)

Blastocyst

Pluripotent: Can become any cell in

body

Implantation

Fate Decision

Gastrulation (day 14) leads toPrimary Germ CellsEndoderm (inner)digestive tract, resp. trackMesoderm (middle)bones, blood cells, heartEctoderm (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 toPrimary Germ CellsEndoderm (inner)digestive tract, resp. trackMesoderm (middle)bones, blood cells, heartEctoderm (outer)skin, CNS

Multipotent: Can become any cell

within a specific germ layer or celllineage

Multipotent

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Somatic Cell

Endoderm Ectoderm Mesoderm

LiverIntestinePancreas

SkinHair

Nerves

BloodMuscleBone

Cartilage

Somaticstem cell

Germ stemcell

Primitivegerm cell

Gametes

PluripotentEmbryonal stem cell

Totipotentstem cells

Pluripotentstem cells

Adult Multipotent

stem cell

Courtesy of Dr F. Prosper Cardoso.DR.T.V.RAO MD 15


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BONE MARROW STEM CELLS

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HOW TO DERIVE AN EMBRYONIC STEM CELL LINE?

Inner cell mass

Day 5-6Blastocyst

Isolate inner cell mass(destroys embryo)ETHICS?

Culture cells

A stem cell line iscomposed of a

population of cellsthat can replicatethemselves forlong periods oftime in vitro(out of the body) An embryonic

stem cellcloneDR.T.V.RAO MD 17


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THE SCIENCE OF STEM CELLS

Stem cells have the ability to continually reproducethemselves while maintaining the capacity to giverise to other more specialized cells.

Stem cells are found at all stages of development,from embryonic stem (ES) cells that candifferentiate into all specialized cells found in thehuman body, to adult stem cells capable of

regenerating their tissue of origin.

Stem cells occur from the earliest stages ofdevelopment and provide the starting material

for every organ and tissues.DR.T.V.RAO MD 18


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EMBRYONIC STEM (ES) CELLS

ES cells arefound at the

blastocyst stage,four to five daysafter the union of

the sperm andegg, before theembryo implants

in the uterus.DR.T.V.RAO MD 19


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ES CELLS ARE "PLURIPOTENT" - I.E. CAPABLE OFFORMING EMBRYONIC TISSUES

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Stem cells may be derived

from autologous,

allogeneic or xenogeneic

sources. Histocompatibility

is prerequisite fortransplantation of

allogeneic stem cells. Fatal

tissue is the best current

tissue source for humanneural stem cells, however

ethical issues are a major

concern.

SOURCE OF STEM CELLS

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C SO C O S


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PLACENTA A SOURCE OF STEMCELLS

Placental stem cells,

like umbilical cord

blood and bone

marrow stem cells,can be used to cure

chronic blood-related

disorders such assickle cell disease,

Thalassemia, and

leukaemia.DR.T.V.RAO MD 23


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REPORT OFPRELIMINARY

RESULTS OFTRANSPLANTATIONUSING PARTIALLY HLA-MISMATCHEDPLACENTAL BLOODFROM UNRELATEDDONORS.

JOANNE KURTZBERG,M.D.ET AL

Placental Blood as a Source of Hematopoietic Stem

Cells for Transplantation into Unrelated Recipients

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UMBILICAL CORD BLOOD STEM CELLTRANSPLANT

Umbilical cord blood

stem cell transplants are

less prone to rejection

than either bone marrowor peripheral blood stem

cells. This is probably

because the cells have

not yet developed thefeatures that can be

recognized and attacked

by the recipient's immune

system DR.T.V.RAO MD 25


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KINDS OF STEM CELLSStem cell type Description Examples

Totipotent Each cell can develop into a

new individual

Cells from early (1-3

days) embryos

Pluripotent Cells can form any (over 200)

cell types

Some cells of blastocyst

(5 to 14 days)

Multipotent Cells differentiated, but can

form a number of other tissues

Fetal tissue, cord blood,

and adult stem cells

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They have the potential toreplace cell tissue that hasbeen damaged ordestroyed by severeillnesses.

They can replicatethemselves over and overfor a very long time.

Understanding how stem

cells develop into healthyand diseased cells willassist the search for cures.

WHATS SO SPECIAL ABOUT STEM CELLS?

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Embryonic(also calledpluripotent) stem cellsare capable of developinginto all the cell types of the

body.

Adult stem cells are lessversatile and more difficultto identify, isolate, and

purify.

TWO KINDS OF STEM CELLS

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EMBRYONIC STEM CELLSEmbryos are formedin labs that helpcouples get

pregnant. An eggand sperm fertilize azygote and areinserted into awomans uterus to

develop into anembryo and thenfetus.

http://biodidac.bio.uottawa.ca/thumbnails/filedet.htm?File_name=HUMN150B&File_type=GIF

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STAGES OF EMBRYOGENESIS

Day 1Fertilized egg

Day 22-cell embryo Day 3-4Multi-cell embryo

Day 5-6BlastocystDay 11-14

Tissue DifferentiationDR.T.V.RAO MD 30


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DERIVATION AND USE OF EMBRYONIC STEMCELL LINES

Isolate 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

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EMBRYONIC STEM CELLS


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EMBRYONIC STEM CELLS:Researchers extract stem cells from a 5-7 days oldblastocyst.

Stem cells can divide in culture to form more of their own kind,

thereby creating a stem cell line.

The research aims to induce these cells to generate healthytissue needed by patients.

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Adult stem cells are calledsomatic or body stem cells.Some people call these adultbecause they are found afteran embryo develops into a

fetus and are no longer anembryonic stem cell. Not onlyadults have adult stemcells! Some organs arebelieved to lack stem cells

and these cells grow andreplace dead cells withmitosis.

ADULT STEM CELLS

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Adult stem cells develop

into a few cell types. These

Multipotent cells are usedin bone-marrow transplants

and will develop into all theblood cells. These cells are

important, but some organs

may not have adult stem

cells and these cells can bedifficult to find

ADULT STEM CELLS

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AUTOLOGOUS STEM CELLS Sources of the patient's

own stem cells(autologous) are either thecells from patient's ownbody or his or her cord

blood. For autologoustransplants physicians nowusually collect stem cellsfrom the peripheral bloodrather than the marrow

This procedure is easier,unlike a bone marrowharvest, it can take placeoutside of an operatingroom and the patient doesnot have to be undergeneral anaesthesia.DR.T.V.RAO MD 35


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Sources of stem cellsfrom another donor(allogeneic) are primarilyrelatives (familial-

allogeneic) or completelyunrelated donors(unrelated-allogeneic).The stem cells in thissituation are extractedfrom either the donor'sbody or cord blood

ALLOGENEIC STEM CELLS

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In this stem cells fromdifferent species aretransplanted, e.g.striatal porcine fetal

ventral mesencephalic(FVM) xenotransplantsfor Parkinson'sdisease. This has nomajor ethical concerns

and a large amount oftissue is available,however life longimmunosupression andrisk of rejection are themajor limitations

XENOGENEIC - STEM CELLS

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HOW DOES CELL THERAPY WORK?

Bone marrow transplants are an example of celltherapy in which the stem cells in a donor's marroware used to replace the blood cells of the victims ofleukemia.

Cell therapy is also being used in experiments to graftnew skincells to treat serious burn victims, and togrow new corneas for the sight-impaired.

In all of these uses, the goal is for the healthy cellsto become integrated into the body and begin tofunction like the patient's own cells.

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WHAT DISEASES CAN BECURED BY STEM CELL THERAPIES

Any disease inwhich there is

tissuedegeneration canbe a potential

candidate for stemcell therapies

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MAJOR PROGRESS IN SEVERAL IMPORTANTHEALTH PROBLEMS

Alzheimers disease

Parkinsons disease

Spinal cord injury

Heart disease

Severe burns

Diabetes

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ALZHEIMERS DISEASE AND CAN STEM


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ALZHEIMERS DISEASE AND CAN STEM

CELLS HELP?

Stem cells could,however, be geneticallymodified so as to deliversubstances to theAlzheimer brain, to stop

cells from dying andstimulate the function ofexisting cells. A recentclinical trial (Phase I) hasshown this approach tobe of some benefit topatients with Alzheimersdisease, by slowing downthe progression of the

disease. DR.T.V.RAO MD 41


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DRUG TESTING

Stem cells could allow scientists totest new drugs using human cell line

which could speed up new drug

development.Only drugs that were safe and had

beneficial effects in cell line testing

would graduate to whole animal or

human testing.

It would allow quicker and safer

development of new drugs.DR.T.V.RAO MD 42


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MAJOR TYPES OF STEM CELLS

The two broad types of

mammalian stem cells are:

embryonic stem cells thatare isolated from the inner

cell mass of blastocysts, andadult stem cells that arefound in adult tissues. In a

developing embryo, stem

cells can differentiate into allof the specialized embryonic

tissues. I

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STEM CELLS ACT AS PROGENITOR CELLS

In adult organisms, stem

cells and progenitorcells act as a repair

system for the body,replenishing specialized

cells, but also maintain

the normal turnover of

regenerative organs,such as blood, skin or

intestinal tissues.

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HISTORY OF ANIMAL CLONINGSince then, animals including mice (1998),

cows (1998), pigs (2000), cats (2001), andrabbits (2002) were successfully cloned.

RABBIT

MOUSE

CAT

Cattle

PIG

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Dolly (sheep) 1 live birth out of 29 clonedembryos

3%

Cloned mice 31 live births out of 2468 clonedembryos

1%

Cloned pigs 5 live births out of 335 clonedembryos 1%

Cloned goats 3 live births out of 85 clonedembryos

3%

Cloned cattle30 live births out of 496 cloned

embryos 6%Cloned cat 1 live birth out of 87 cloned

embryos1%

Cloned rabbits 6 live births out of 371 of cloned

embryos

1%

HOW SUCCESSFUL WAS ANIMALCLONING? VERY LOW (~1-3%)

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FIRST SUCCESS OF HUMAN EMBRYOCLONING

On February 12, 2004, SouthKorean scientists, Dr. Woo SukHwang and Dr. Shin Young Moon ofSeoul National University, reported thesuccessful creation of30 cloned

human embryos developed to theblastocyst stage and then destroyedby stem cell extraction,yielding one

embryonic stem cell line.DR.T.V.RAO MD 47


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Tens of thousands offrozen embryos areroutinely destroyed whencouples finish theirtreatment.

These surplus embryoscan be used to producestem cells.

Regenerative medicalresearch aims to develop

these cells into new,healthy tissue to healsevere illnesses.

SOURCE OF STEM CELLS FOR MEDICALTHERAPIES

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STEM CELL RESEARCH WORLDWIDE

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ADULT MU TIPOTENT STEM CELLS


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ADULT MULTIPOTENT STEM CELLS

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Adult Stem Cells

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AUTOLOGOUS STEM CELLS

While most blood stem cells

reside in the bone marrow, a

small number are present in

the bloodstream. These

Multipotent peripheral bloodstem cells, or PBSCs, can be

used just like bone marrow

stem cells to treat leukaemia,

other cancers and variousblood disorders

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S l ti


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multipoten

t

Speculation

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TREATMENTS BECOMES SPECIFIC

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APPLICATIONS OF STEM CELLS

Cell Replacement Therapies Cells could be stimulated to develop into specialized

cells that represent renewable sources of cells and

tissue for transplantation.

Cell replacement therapy could treat injuries andvarious genetic and degenerative conditions includingmuscular dystrophies, retinal degeneration, Alzheimerdisease, Parkinson's disease, arthritis, diabetes, spinalcord injuries, and blood disorders such as hemophilia.

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UNDERSTANDING CELL


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UNDERSTANDING CELLSPECIALIZATION

Studying human pluripotent stem cells can lead tothe identification of factors responsible fordifferentiation of stem cells into specialized cell

types. these factors may ultimately be used to drive tissue

regeneration and repair if administered therapeutically.

This work will provide basic knowledge on celldetermination and differentiation, humandevelopment, genomic imprinting and somatic cellaging.

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DEVELOPMENT AND TESTING OF


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DEVELOPMENT AND TESTING OFDRUGS

Researchers couldstudy the beneficialand toxic effects of

new medications onhuman pluripotentstem cells that havebeen developed to

mimic the diseaseprocesses.

DR.T.V.RAO MD 57

CAN SEX MAKE DIFFERENCE IN STEM


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CAN SEX MAKE DIFFERENCE IN STEM

CELL THERAPY ? Are there sex-specific

differences in the biology ofstem cells? (short-long term

How do sex-specificdifferences play out in termsof self-renewal anddifferentiation? (mid-longterm)

Is there existing evidencethat the sex of stem cellsaffects success of thetransplant?

XX vs.

XYDR.T.V.RAO MD 58


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STEM CELLS BLINDNESS

In clinical trials atMoorfields EyeHospital in London,

surgeons restored eyesight for six patientswho lost their sightafter chemical

accidents and geneticdiseases. The patientswent under successfulstem-cell transplant.

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LIMBAL STEM CELL THERAPY

The treatment is known aslimbal stem cell therapy, andthe patients who received thetreatment suffered fromchemical burn or geneticdisease know as aniridia

By replacing the limbalstem cells, the cornea beginsto clear up as the cells are

replaced with the healthytransparent layer again.

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Research in stem cells hasopened up new horizons in thearea of treatment of disorderssuch as stroke, epilepsy, neuro-degeneration and trauma.Current research is aimed atfinding the appropriate source ofstem cells for a given indication,ways of expanding andperpetuating these cells inculture, best route ofadministration of these cells andmethods to overcome rejection

CURRENT POSSIBLE USES

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POSSIBLE USES OF STEM CELL TECHNOLOGY

Replaceable

tissues/organs

Repair of defective cell

types

Delivery of genetic

therapies

Deliverychemotherapeutic agents

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FUTURE MAKING CELLS AND


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FUTUREMAKING CELLS ANDREPLACING THE DISEASED CELLS ?

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DR.T.V.RAO MD

STEM CELL DEBATE

Some people oppose stem cell research becausethey believe that the 4-5 day old ball of cells is aliving human being. What some do not understand is

that unused embryos are trashed regardless. Manypeople, religious and non-religious, believe it is betterto use these embryos for research on how to curehuman diseases rather than to just trash them without

purpose. The underlying issue is the personal beliefwhen life actually begins.

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OBSTACLES OF STEM CELL RESEARCH

How to find the right type of stem cells?

How to put the stem cells into the right place?

Will the stem cells perform the desiredfunction in the body?

Differentiation protocols for many cell types

have not been developed.

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EMBRYONIC STEM CELLS ARE UNSTABLE ANDMUTATE IN CULTURE

Like ordinary cells,

stem cells

accumulate

significant numbers

ofmutationsover

time, including

several that could

cause them to

become tumors.DR.T.V.RAO MD

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Harvesting ES cellsdestroys the blast cyst

This is murder

ES cell researchrequires human cells

Could create acommercial market forhuman cells

This devalues life

ETHICAL DEBATE

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Service

DR.T.V.RAO MD 68

DESTROYING LIFE TO CURE SOME


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If stem cells have suchpotential to relieve

suffering, why are so many

people so upset about their

use? The reason is that themost powerful type of stem

cell embryonic stem(ES) cells can only beobtained from human

embryos. Many people

think that it's wrong to

create and destroy human

embryos to treat disease

DESTROYING LIFE TO CURE SOMEONEETHICAL ?

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RELIGIOUS DEBATE OVER HARVESTING


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RELIGIOUS DEBATE OVER HARVESTINGEMBRYONIC STEM CELLS

The pro-life group generallybelieves that:

Personhood happens at, or shortlyafter, conception.

Thus, they consider the removal ofstem cells from an embryo -- aprocedure which kills the stem cells -- to be a form of murder of a humanbeing.

They argue that no potential healthbenefits to even hundreds of millionsof people can justify the murder ofother humans.

Day 5-6Blastocyst

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RELIGIOUS DEBATE OVER HARVESTING


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RELIGIOUS DEBATE OVER HARVESTINGEMBRYONIC STEM CELLS

The pro-choice group generallybelieves that:

Personhood is attained much later inpregnancy, perhaps when the fetal brain

develops consciousness during the thirdtrimester.

Thus, extracting stem cells from an fiveor ten-day old pre-embryo is notmurder.

Killing a pre-embryo, which is onlya potential human being, is

justified if it has the potential tocure diseases and extend the livesof people.

Day 5-6Blastocyst

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WHY WE SHOULD SUPPORT


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WHY WE SHOULD SUPPORTCAN HELP SEVERAL DISABLED

Human embryonic

stem cell (HESC)

research offers great

promise of cures forotherwise incurable

conditions: spinal cord

injuries, ALS,Alzheimers,

Parkinsons, etc.

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Arguments for and againsthuman cloning research.

Should we ban human

cloning? Why investors are

moving away from humancloning and why human

cloning now looks a last-

century way to fight

disease. Why some people

want to clone themselves

or even to clone the dead.

SHALL BE CLONE HUMANS ?

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FUTURE APPLICATIONS

Stem Cells may one day help scientists to regeneratecells lost in diseases like:

Repair heart muscle after a heart attack

Pancreas cells lost in diabetes

Neurons lost in Alzheimers

Retinal cells causing blindness

Understand the cell growths of cancers Help organ transplantation

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S C O S C S S OG SS G


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RESEARCH ON STEM CELLS IS PROGRESSING INSPITE OF SEVERAL RESTRICTIONS

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ARE WE CROSSING OUR LIMITS IN SCIENCE ???

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Programme created by Dr.T.V.Rao MD from

several web based and documented information

for Medical and Paramedical Professionals inthe Developing World

Email

[email protected]

Stem Cells and Progress of Science

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