Cell Proliferation and Differentiation New

8/3/2019 Cell Proliferation and Differentiation New

1/38

By

Prof. Dr Shefaa El Sawy

Prof Dr Safinaz Safwat

Cell proliferation anddifferentiation


2/38

Cell proliferation

An increase in the number of

cells as a result of cellgrowth and cell division


3/38

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.


4/38

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


5/38

As cells differentiate, their rate ofproliferation usually decreases, and

many cells in adult animals arearrested in the G0 stage of the cellcycle.

Cell


6/38

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


7/38

Constant number of cells

in adult tissues andorgans.

Cell proliferation = cell death


8/38

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)


9/38

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.


10/38

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


11/38

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


Differen

tiate


12/38

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


Differen

tiate


13/38

1. blood cells.

1. Epithelial cellsof the skin.


14/38

Stem Cells Definition

1. They Areundifferentiated

mastercell that donot yethave aspecificfunction

Stem cell

Stem cell

Self

-ren

ewal


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.


15/38

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


16/38


17/38

Factors that regulate stem cell within the niche

1. cell-cell interactions between stem cells

1. interactions between stem cells and

adhesion molecules


18/38

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


19/38

4. extracellular matrixcomponents

5. the oxygen tension

5. growth factors

5. Cytokines

8. physiochemical nature of theenvironment including the pH, ionicstrength


20/38

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


21/38

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


22/38

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.


23/38

According to their potency (Differentiation capability), stem

cells can be classified into different cell types:

Types of stem cells


24/38

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


25/38

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).


26/38

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


27/38

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


28/38

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.


29/38

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


30/38

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.)


31/38

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


32/38

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


33/38

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


34/38

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.


35/38

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.


36/38

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


37/38

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


38/38

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.

Documents

Cell Proliferation and Differentiation New