cell proliferation and differentiation new
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By
Prof. Dr Shefaa El Sawy
Prof Dr Safinaz Safwat
Cell proliferation anddifferentiation
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Cell proliferation
An increase in the number of
cells as a result of cellgrowth and cell division
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Unspecializedcell
Specialized cell(e.g., white blood cell)
Differen
tiate
Cell differentiation:
The processes
involved incommitment of acell to a specificfate.
Or
The processwhereby relatively
unspecialized cells,e.g. embryonic orregenerative cells,acquire specialized
structural and/or
Specialized cell havingspecific structural,
functional, and biochemicalproperties.
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Early development ischaracterized by therapid proliferation ofembryonic cells, whichthen differentiate to
produce the manyspecialized types ofcells that make up thetissues and organs ofmulticellular animals.
Cell proliferation inembryo
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As cells differentiate, their rate ofproliferation usually decreases, and
many cells in adult animals arearrested in the G0 stage of the cellcycle.
Cell
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Most cells in adult animalsare arrested in the G0 stage
& resume proliferation ondemand
Few cells cannotenter the cycle
Afterdifferentiatio
n
Some cellscontinuously
cycling cells toreplace cells that
have a high rate of
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Constant number of cells
in adult tissues andorgans.
Cell proliferation = cell death
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Cell proliferation in adult
The cells of adult animals can be grouped intothree general categories:
1. Tissues with permanent cells : Static cellpopulation or non-dividing.
1. Renewal by simple duplication of existingsimple cells (stable cell population orquiescent cells.
1. Renewal by stem cells (continuouslydivining or labile cells)
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Static cell population ornon-dividing.
They leave the cellcycle to performspecializedfunctions.
These cells are no
longer capable ofcell division.
They would not bereplaced if injuredor lost
TD Terminaldifferentiatedcell such as1. 1- neuron2. cardiac
muscles3. Lens cells4. skeletal
muscles.
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Stable cell population orquiescent cells
They do not usuallydivide, and considered tobe in G0 stage.
They can be triggered todivide by appropriatesignals as injury.
These cells divide to givepairs of daughter cells ofthe same type.
1. smoothmuscle
cells.2. endothelial
cells.3. epithelial
cells ofmost
internalorgans.
simpleduplication ofexisting cells
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Renewal by stem cells =continuously divining or
labile cells The fully
differentiated cellsdo not proliferatebut are replaced bythe proliferation of
less differentiatedcells, called stemcells
Stem cell
Stem cell
Self-
renew
al
Specialized cell(e.g., white blood cell)
Differen
tiate
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Renewal by stem cells =continuously divining or
labile cells Serving as a source
for the productionof differentiatedcells throughoutlife.
They include allcells that haveshort life span.
Stem cell
Stem cell
Self-
renew
al
Specialized cell(e.g., white blood cell)
Differen
tiate
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1. blood cells.
1. Epithelial cellsof the skin.
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Stem Cells Definition
1. They Areundifferentiated
mastercell that donot yethave aspecificfunction
Stem cell
Stem cell
Self
-ren
ewal
Specialized cell(e.g., white blood cell)
Differen
tiate
2. Canundergounlimited
cell
division(self-
renewal)
under proper conditions
3-They are found in all multi-
cellular organisms that
retain the ability to produce
through mitosis both a self-
renewing stem cell and a
second cell with the
capacity to differentiate
into more specialized cells.
They are primal cells which arethe source, or stem, for all ofthe specialized cells that form
organs and tissues.
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functions ofstem cells
In a developing embryo:
differentiate into all of the
specialized embryonic tissues.
1. Play a key role in thedevelopment of
multicellular organism.
1. Providing cells for renewal
and regeneration of adult
tissues.
In adult organisms: act as a
repair system for the body
giving rise of specialized
cells.
Required to replace
differentiated cells thatcannot divide themselves if
the terminal state of cell
differentiation is
incompatible with cell
division.outer most layer of
Striated muscle
red blood cells
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Factors that regulate stem cell within the niche
1. cell-cell interactions between stem cells
1. interactions between stem cells and
adhesion molecules
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Niche cells anchor stem cells with adherensjunctions to provide cell surface and secreteproteins activating signaling pathways to regulatethe cell cycle of the stem cell.
Some of these factors stimulate division; others
3. interactions between stem cells andneighboring stromal niche cells
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4. extracellular matrixcomponents
5. the oxygen tension
5. growth factors
5. Cytokines
8. physiochemical nature of theenvironment including the pH, ionicstrength
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Embryonic stem cell niche
During embryonic development, variousniche factors act on embryonic stem cells toinduce their proliferation or differentiation
Click to edit Master text stylesSecond level Third level Fourth level
Fifth level
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Maintain adult stem cells in a quiescent state, until needed:stem cell storage.
In tissue injury, the surrounding microenvironment activelygives signals to stem cells to either promote self renewal ordifferentiation to form new tissues.
Stem cell niches occur in every organ in the body that canregenerate this organ if damaged (organ specific stem cells)
Adult stem cell niche
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STEM CELL PROPERTIES1- Self-renewal: the ability to go through numerous
cycles of cell division while maintaining the
undifferentiated state.
2- Potency: the capacity to differentiate into
different cell types (either totipotent or pluripotent).
Multipotent or unipotent progenitor cells are
also referred to as stem cells.
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According to their potency (Differentiation capability), stem
cells can be classified into different cell types:
Types of stem cells
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Stages of Embryogenesis
Fertilized egg
2-cell embryo Multi-cell embryo
Day 5-6BlastocystDay 11-14
Tissue Differentiation
spermEgg
Inner cells(forms fetus)
Outer cells(forms placenta)
Morula
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Totipotent stem cells:
Totipotent means entire.
They have the potential to generate
all the cells and tissues that make up
an embryo.
Can construct a complete, viable,
organism.
Produced from the fusion of an egg
and sperm cell (first few divisions;
morula's cells).
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Pluripotent stem cells
Pluri means several or many.They are derived from the inner cellmass of the blastocyst
They can differentiate into allderivatives of the three primary
germ layers: ectoderm, endoderm,and mesoderm.
They can form most types of tissuefound in the human body, theycannot form an organism
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Multipotent stem cells:can produce only cells of a
closely related family of cells.
1. hematopoietic stem cells
differentiate into red blood
cells, white blood cells, and
platelets.
2. epithelial stem cells that give
rise to the various types of
skin cells.
Most adult stem cells belong to this category
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Unipotent cells:Means one.
Can produce onlyone cell type, buthave the propertyof self-renewal
whichdistinguishesthem from non-stem cells.
eg.: -Musclesatellite cellsthat contribute todifferentiatedmuscle tissue.
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SOURCES OF STEM CELLS FOR(Where do stem cells come from?)
Four potential sources for stem cells
1. Embryonic stem cells (ES cells).
2. Adult stem cells.
3. Amniotic fluid stem cells.
4. Induced pluripotent stem cell.
S f St
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Sources of Stem
Cells
Type Source potency Differentiated cell type
1- Embryonicstem cells
4- 5days old embryo(blastocyst)
pluripotent stem cells Any of the 220 cell typespresent in the humanbody (e.g., skin cells,liver cells, etc.)
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Advantage of use of ESC:
1. They can divide into more stem cells or they can specialize and become any type of bodycell so they are used to regenerate or repair many diseased tissue and organs.
2. Represent an ideal source for tissue regeneration as they are immunologically inactive.
The limited use of ES cells in stem cell therapy is due to:
1. Ethical restriction as they come from destroyed human embryos.
2. Being pluripotent (requiring specific signals for correct differentiation) carry a highincidence for the development of tumors.
T pes of Stem
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Types of Stem
Cells
Type Source potency Differentiat
ed cell type
2- Adult stem cells
AOrgan
specific stemcell
Refer to any cellfound in a developedorganism that hasthe properties ofstem cells ( inchildren and adult)
Most are multipotentstem cells
Develop into the samecell types. E.g., bloodstem cells can developinto several blood celltypes, but cannotdevelop into brain,kidney, or liver cells.
BUmbilical cord
stem
Taken fromumbilical cord
blood
pluripotent stemcells
CFetal stemcells
Taken from organs offetuses at a laterstage ofdevelopment
Pluripotent ormultipotentstem cells
Types of Stem
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Types of Stem
CellsType Source potency Differentiat
ed cell type
3- Amnioticfluid stem
cells
Resided in floatsfreely in the
amniotic fluid ofpregnant women
multipotentstem cells
Develop intoclosely related
family of cells.
4- Inducedpluripotentstem cell
Dedifferentiatedadult somaticcells through
alteration ofgenes
pluripotentstem cells
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Amniotic fluid stem cells:Advantage of usage:
1.The cells, shed by the developing fetus and easily
retrieved during routine prenatal testing,.
2.Easier to maintain in laboratory dishes thanembryonic stem cells.
3.The cells are a genetic match to the developing fetuswill not be rejected if used to treat birth defects
in that newborn.
4.The cells could be frozen, providing a personalizedtissue bank for use later in life.
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Induced pluripotent stemcellAdvantage:
new technique mayhelp researchers toavoid the limitations ofembryonic stem cells.
Disadvantage:The technique involves
processes that may notbe safe for use in people.
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The uses of stem cells and theirclinical applications:
Stem cell forms thecore of a new field"regenerativemedicine".
1. In transplanttherapy: e.g. toreplace or restoretissue that hasbeen damaged bydisease or injury.
cell culture ofadult stem cells
R ti b i ll d i d f
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2. Regenerating bone using cells derived frombone marrow stroma.
3. Treatment of type 1 diabetes by developinginsulin-producing cells.
4. Repairing damaged heart muscle following aheart ischemia.
5. Treatment of Alzhiemers disease.6. Treatment of leukemia
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7. Used to study and screen new therapeutic drugs
8. Develop model systems to study normal growth and identify thecauses of birth defects.
9. Advance knowledge about how an organism develops from a single
cell and how healthy cells replace damaged cells in adult organisms.
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