2014 02 stem cell introduction 860461

8/17/2019 2014 02 Stem Cell Introduction 860461

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Stem Cell Basics


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Stem cell

remarkable potential to develop intomany different cell types

Serving as a sort of repair systemfor the body

divide without limits become another type of cell with a

more specialized function, such as amuscle cell, a red blood cell, or abrain cell.


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introduction This is a promising area of sciences how an organism develops from a

single cell how healthy cells replace damaged

cells in adult organisms. regenerative or reparative

medicine : investigate the possibility of cell-

based therapies to treat disease


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What are stem cells and why are they

important?

Stem cells have two importantcharacteristics that distinguish them fromother types of cells

#they are unspecialized cells #they can be induced to become cellswith special functions heart, pancreas

tow kind of cells from human andanimals

!mbryonic stem cell and adult stem cell There is a different functions and

characteristic


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"rom early mouse embryos , $ y.ago

%&&' it is isolated from human embryos :human embryonic stemcells

(y way of in vitro fertilization

procedures.


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Stem cells are important for living organismsbecause :

)n the blastocyst stem cells give multiplespecialized cell types

)n some adult tissues, adult stem cells generatereplacements for cells that are lost throughnormal wear and tear, in*ury, or disease.

)t has been hypothesized that stem cells may, atsome point in the future, become the basis for

treating diseases such as +arkinsons disease,diabetes, and heart disease.


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(y studding stem cell

they can learn about their essentialproperties and what makes them different

from specialized cell types it may become possible to use the cells

not *ust in cell-based therapies,

but also for screening new drugs andtoins and understanding birth defects.


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the fundamental properties ofstem cells, which include:

%-determining precisely how stemcells remain unspecialized and selfrenewing for many years and

-identifying the signals that

cause stem cells to becomespecialized cells.


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What are the unique properties of all

stem cells?

/ll stem cells have 0 generalproperties :

%. capable of dividing and renewingthemselves for long periods

. they are unspecialized

0. they can give rise to specialized celltypes.


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Scientists are trying to understand two

fundamental properties

1why can embryonic stem cells proliferate for a year or more in thelaboratory without differentiating, but most adult stem cells cannot

1what are the factors in living organisms that normally regulate stem cellproliferation and self-renewal2

the answers

understand how cell proliferationis regulated during normal embryonic development

during the abnormal cell division that leads to cancer

such information would enable scientists to grow embryonic andadult stem cells more efficiently in the laboratory.


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Stem cells are unspecialized.

There is no tissue-specific structures thatallow it to perform specialized functions

3owever, unspecialized stem cells can give riseto specialized cells, including heart muscle cells, blood cells, or nerve cells.


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Stem cells are capable of dividing and

renewing themselves for long periods

stem cells may replicate many times unlike musclecells, blood cells, or nerve cells

That can yield millions of cells in the laboratory

)f the resulting cells continue to be unspecialized,like the parent stem cells, the cells are said to becapable of long-term self-renewal.


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Stem cells can give rise to specialized

cells

4ifferentiation : unspecialized stem cells

specialized cells

The internal signals are controlled by a cells genes

They are interspersed across long strands of 45/, andcarry coded instructions for all the structures and functionsof a cell

trigger


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The eternal signals for cell differentiation include

chemicals secreted by other cells

physical contact with neighboring cells

and certain molecules in the microenvironment 6uestions remain: are the internal and eternal signals for cell differentiation similar

for all kinds of stem cells2

7an specific sets of signals be identified that promotedifferentiation into specific cell types2

the answers may lead to find new ways of controllingstem cell differentiation in the laboratory, thereby growingcells or tissues that can be used for specific purposes

cell-based therapies.


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/dult stem cells typically generate the cell types ofthe tissue in which they reside

)n bon marrow / blood-forming adult stem cell8hematopoietic stem cell 9 gives red, white, and

platelets. only ecently it is raised the possibility that stem cells from

one tissue may be able to give rise to cell types of acompletely different tissue

blood cell neurons ;liver cells heart muscle.

plasticity


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Stem Cell Basics


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Stem Cell Basics

The fertilized eggs are not derived fromeggs fertilized in a womans body theyare donated for research purposes withinformed consent of the donors by

(. 3ow are embryonic stem cells grownin the laboratory2

cellculture

)nner cell mass

)n nutrient culture medium

"eeder layer

subculturing

passage , after =month or more the

original 0$ cells of the inner cell massyield millions of embryonic stem cellscalled embryonic stem cell line

(y pluripotent 8 proliferation without

differentiation 9


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C. What laboratory tests are used to identify embryonic stem cells?

characterization : test the cells to see whether theyehibit the fundamental properties that make themembryonic stem cells

>any kind of testes :1 growing and subculturing the stem cellsfor many months microscope inspection for the healthy and

undifferentiated of cells. 1 using specific techni?ues to determine the presence

of surface markers that are found only on undifferentiated cells 1presence of a protein called @ct-A ; a transcription

factor ;it helps turn genes on and off at the right time ;it is an important part of the processes of cell differentiation andembryonic development.

1eamining the chromosomes under amicroscope ; the chromosomes are damaged 2;thenumber of chromosomes has changed 2;)t does not detectgenetic mutations in the cells.


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1determining whether the cells can be subcultured after freezing,thawing, and replating

1testing whether the human embryonic stem cells are pluripotentby :

%9 allowing the cells to differentiate spontaneously in cell culture

9 manipulating the cells so they will differentiate to form specific celltypes

09 in*ecting the cells into an immunosuppressed mouse to test for theformation of a benign tumor called a teratoma

1Teratomas typically contain a miture of many differentiated or partly differentiatedcell types

1an indication that the embryonic stem cells are capable of differentiating into multiple

cell types.


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scientists try to control the differentiation of embryonic stem cells They change the chemical composition of the culture medium ;

alter the surface of the culture dish ;

modify the cells by inserting specific genes ;

Through years of eperimentation scientists have established some basic

protocols or BrecipesB for the directed differentiation of embryonic stemcells into some specific cell types

)f scientists can reliably direct the differentiation of embryonic stem cellsinto specific cell types, they may be able to use the resulting,differentiated cells to treat certain diseases at some point in the future.4iseases that might be treated by transplanting cells generated from

human embryonic stem cells include +arkinsons disease, diabetes,

traumatic spinal cord in*ury, +urkin*e cell degeneration,4uchennes muscular dystrophy, heart disease, and vision andhearing loss.


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What are adult stem cells?

undifferentiated cell found among differentiatedcells in a tissue or organ

7an renew it self

7an differentiates to yield the ma*or specialized celltypes of the tissue or organ

The primary roles of adult stem cells in a livingorganism are to maintain and repair the tissue inwhich they are found.

somatic stem cell ,, Cnlike embryonic stem cells , the origin is unknown


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What are adult stem cells?

7an adult stem cell been used in transplant 2

adult blood forming stem cells from bone marrowhave been used in transplants for 0$ years

the ability to differentiate into a number of differentcell types

these cells may become the basis of therapies formany serious common diseases.

)n the %&=$shematopoietic stem cells

bone marrowstromal cells

Stromal cells are a mied cell population that generates bone,cartilage, fat, and fibrousconnective tissue


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A. Where are adult stem cells found and what do

they normally do?

most scientists believed that new nerve cells could not be generated in theadult brain.

)t was not until the %&&$s that scientists agreed that the adult brain doescontain stem cells that are able to generate the brains three ma*or celltypesDastrocytes and oligodendrocytes, which are non-neuronal cells,and neurons, or nerve cells.

adult stem cells have been identified in many organs and tissues

very small number ; reside in a specific area ;they may remain?uiescent 8non-dividing9 for many years

until they are activated by disease or tissue in*ury

laboratories are trying to find ways to grow adult stem cells in

cell culture manipulate them to generate specific cell types so they can be

used to treat in*ury or disease

+arkinsons patients ;type ) diabetes ;heart attack


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B. What tests are used for identifying adult stem

cells?

There is no agreement about identify E test S7 0 methods :18%9 labeling the cells in a living tissue with molecular markers and then

determining the specialized cell types they generate 1

1 89 removing the cells from a living animal

labeling them in cell culture

transplanting them back into another animal to determine whetherthe cells repopulate their tissue of origin 1

1809 isolating the cells

growing them in cell culture and manipulating them

often by adding growth factors or introducing new genes

to determine what differentiated cells types they can become. /S7 cam make a clone8 line of genetically identical cells9 in the tissue reside

by infecting adult stem cells with a virus that gives a uni?ue identifier to eachindividual cell, scientists have been able to demonstrate that individual adult stem cellclones have the ability to repopulate in*ured tissues in a living animal.


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C. What is known about adult stem

cell differentiation?


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4ifferentiation

transdifferentiation ; plasticity

3ematopoietic stem cells F.

mesenchymal stem cells8 bon marrow S79 F..

neural stem cells F..

!pithelial stem cells

Skin stem cells epidermis3air follicle


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transdifferentiation / plasticity

certain adult stem cell types are pluripotent

eamples of adult stem cell plasticity that have beenreported during the past few years:

3ematopoietic stem cells 0ma*or type of

brain ;skeletal muscle ;cardiac muscl;liver cell; (one marrow stromal cells may differentiate into : cardiac; skeletal muscle

(rain stem cells may differentiate into :

blood ; skeletal muscle 7urrent research is aimed at determining the mechanisms that underlie adult stem cellplasticity. )f such mechanisms can be identified and controlled, eisting stem cells froma healthy tissue might be induced to repopulate and repair a diseased tissue


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D. What are the key questions about adult stem

cells?

>any important ?uestions about adult stem cells remain to be answered They include:

3ow many kinds of adult stem cells eist, and in which tissues do they eist2


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V. What are the similarities and differences

between embryonic and adult stem cells?

!mbryonic stem cells are pluripotent

Garge numbers of embryonic stem cellscan be relatively easily grown in culture

large numbers of cells are needed for stem cellreplacement therapies

!mbryonic stem cells from a donorintroduced into a patient could causetransplant re*ection

/dult stem cells are generally limited 3owever, adult stem cell plasticity may eist

adult stem cells are rare in maturetissues

The use of own adult stem cell would

not be re*ected by immune system


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V. What are the potential uses of human stem cells

and the obstacles that must be o!ercome before

these potential uses will be reali"ed?

>ay of ways and many pf hurdles identify how undifferentiated stem cells become differentiated Scientists know that turning genes on and off is central to this process abnormal cell division and differentiation 7ancer and birth defects H other serious conditions

/ better understanding of the genetic and molecular controls of these processes how such diseases arise and new strategies for therapy arise hurdle : scientists do not yet fully understand the signals that turn

specific genes on and off to influence the differentiation of the stem cell.

used to test new drugs: safety differentiated , anti-tumor drugs screen drugs effectively but identical +erhaps the most important potential application of human stem cells is the generation

of cells and tissues that could be used for cell-based therapies Stem cell directed to differentiate into specific cell types for replacement cells and

tissues parkinson’s II Alzheimer's II spinal cord injury II stroke II burns IIheart I diabetes II osteoarthritis II rheumatoid arthritis


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#or e$ample it may be possible to direct the differentiation of embryonic stemc. or adult bon marrow cell into heart muscle cell % cell culture&


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)n type J diabetes can be treated "or successful cell-based treatment , stem c. must be : proliferate etensively and generate sufficient ?uantities

of tissue

4ifferentiate into the desired cell type8s9 Survive in recipient after transplant )ntegrate into the surrounding tissue after transplant "unction appropriately for the duration of the recipientKs

life /void harming the recipient in any way Tissuse shouldKnt be re*ected The promise of stem cell therapies is an eicting one Significant technical hurdles remain111


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'( support research for

embryonic stem cell line

+roduced by dr. Salim DAGHER

4epartment of 3ealthand 3uman Se
http://www.os.dhhs.gov/http://usa.gov/http://www.os.dhhs.gov/http://www.nih.gov/http://www.os.dhhs.gov/

2014 02 stem cell introduction 860461

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