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Stem Cells
Stem Cell – Definition
• A cell that has the ability to continuously divide and
differentiate (develop) into various other kind(s) of
cells/tissues
• Stem cells are different from other cells of the body in that
they have the ability to differentiate into other cell/tissue
types. This ability allows them to replace cells that have died.
With this ability, they have been used to replace defective
cells/tissues in patients who have certain diseases or defects.
Stem Cell Characteristics
•
‘Blank cells’ (unspecialized)
•
Capable of dividing and renewing
themselves for long periods of time
(proliferation and renewal)
•
Have the potential to give rise to
specialized cell types (differentiation)
Kinds of Stem Cells
Stem cell
type
Totipotent
Pluripotent
Multipotent
Description
Examples
Cells from early
Each cell can develop
(1-3 days)
into a new individual
embryos
Some cells of
Cells can form any (over
blastocyst (5 to 14
200) cell types
days)
Cells differentiated, but
can form a number of
other tissues
Fetal tissue, cord
blood, and adult
stem cells
Stem cells can be classified into three broad categories,
based on their ability to differentiate. Totipotent stem
cells are found only in early embryos. Each cell can
form a complete organism (e.g., identical twins).
Pluripotent stem cells exist in the undifferentiated
inner cell mass of the blastocyst and can form any of
the over 200 different cell types found in the body.
Multipotent stem cells are derived from fetal tissue,
cord blood and adult stem cells. Although their ability
to differentiate is more limited than pluripotent stem
cells, they already have a track record of success in
cell-based therapies. Here is a current list of the
sources of stem cells:
1.Embryonic stem cells - are harvested from the inner cell
mass of the blastocyst seven to ten days after fertilization.
2.Fetal stem cells - are taken from the germline tissues that
will make up the gonads of aborted fetuses.
3.Umbilical cord stem cells - Umbilical cord blood contains
stem cells similar to those found in bone marrow.
4.Placenta derived stem cells - up to ten times as many
stem cells can be harvested from a placenta as from cord
blood.
5.Adult stem cells - Many adult tissues contain stem cells
that can be isolated.
This cell
Can form the
Embryo and placenta
This cell
Can just form the
embryo
Fully mature
Kinds of Stem Cells
Embryonic stem cells
• five to six-day-old embryo
• Tabula rasa
Embryonic germ cells
• derived from the part of a human embryo or fetus
that will ultimately produce eggs or sperm
(gametes).
Adult stem cells
• undifferentiated cells found among specialized or
differentiated cells in a tissue or organ after birth
• appear to have a more restricted ability to produce
different cell types and to self-renew.
Pluripotent Stem Cells –
more potential to become any
type of cell
Multipotent stem cells
• Multipotent
stem cells –
limited in what
the cells can
become
Adult Stem Cells
An undifferentiated cells found
among specialized or differentiated
cells in a tissue or organ after birth
•
•
•
•
•
Skin
Fat Cells
Bone marrow
Brain
Many other organs
& tissues
Induced Pluripotent Stem Cells
Bone Marrow
• Found in spongy bone where blood cells form
• Used to replace damaged or destroyed bone
marrow with healthy bone marrow stem cells.
• treat patients diagnosed with leukemia, aplastic
anemia, and lymphomas
• Need a greater histological immunocompatibility
Blood Cell Formation
Umbilical cord stem cells
•
•
•
•
•
Also Known as Wharton’s Jelly
Adult stem cells of infant origin
Less invasive than bone marrow
Greater compatibility
Less expensive
Umbilical cord stem cells
Three important functions:
1. Plasticity: Potential to change
into other cell types like nerve
cells
2. Homing: To travel to the site of
tissue damage
3. Engraftment: To unite with other
tissues
Stem Cell Applications
• Tissue repair
- nerve, heart, muscle, organ,
skin
• Cancers
• Autoimmune diseases
- diabetes, rheumatoid arthritis,
MS
Why is Stem Cell Research So Important
to All of Us?
Stem cells can replace diseased or
damaged cells
Stem cells allow us to study
development and genetics
Stem cells can be used to test different
substances (drugs and chemicals)
Terminology:
STEM CELL- cell which can make exact copies of
itself indefinitely, can differentiate, and produce
specialized cells for various tissues of body.
TOTIPOTENT- can become any kind of cell Early
Embryonic SC
PLURIPOTENT- almost any kind of cell Blastocyst
Embryonic SC
MULTIPOTENT- limited range of cell types
Adult SC: nerve cells, blood cells, muscle cells, bone
and skin cells.
Potency: A measure of how many types of specialized
cell a stem cell can make
Pluripotent Can make all types of specialized cells in
the body Embryonic stem cells are pluripotent
Multipotent Can make multiple types of specialized
cells, but not all types Tissue stem cells are multipotent
APOPTOSIS
INTRODUCTION
Cell death by injury
-Mechanical damage
-Exposure to toxic chemicals
Cell death by suicide
-Internal signals
-External signals
Apoptosis or programmed cell death, is carefully
coordinated collapse of cell, protein degradation ,
DNA fragmentation followed by rapid engulfment of
corpses by neighbouring cells.
Essential part of life for every multicellular organism
from worms to humans.
Apoptosis plays a major role from embryonic
development to senescence.
Why should a cell commit suicide?
Apoptosis is needed for proper development
Examples:
– The resorption of the tadpole tail
– The formation of the fingers and toes of the fetus
– The sloughing off of the inner lining of the uterus
– The formation of the proper connections between neurons in the brain
Apoptosis is needed to destroy cells
Examples:
– Cells infected with viruses
– Cells of the immune system
– Cells with DNA damage
– Cancer cells
What makes a cell decide to commit suicide?
Withdrawal of positive signals
examples :
– growth factors for neurons
– Interleukin-2 (IL-2)
Receipt of negative signals
examples :
– increased levels of oxidants within the cell
– damage to DNA by oxidants
– death activators :
• Tumor necrosis factor alpha (TNF-)
• Lymphotoxin (TNF-β)
• Fas ligand (FasL)
Definition
Apoptosis is a peculiar well controlled
individual cell death that is caspase mediated
and leads to fragmentation of the cell and
organelles into numerous small buds, which
are then engulfed by macrophages without
surrounding inflammation.
Apoptosis, or programmed cell death, is a normal component
of the development and health of multicellular organisms.
Cells die in response to a variety of stimuli and during
apoptosis they do so in a controlled, regulated fashion. This
makes apoptosis distinct from another form of cell death
called necrosis in which uncontrolled cell death leads to lysis
of cells, inflammatory responses and, potentially, to serious
health problems. Apoptosis, by contrast, is a process in which
cells play an active role in their own death (which is why
apoptosis is often referred to as cell suicide).
Upon receiving specific signals instructing the cells to undergo
apoptosis a number of distinctive changes occur in the cell. A
family of proteins known as caspases are typically activated in
the early stages of apoptosis. These proteins breakdown or
cleave key cellular components that are required for normal
cellular function including structural proteins in the
cytoskeleton and nuclear proteins such as DNA repair
enzymes. The caspases can also activate other degradative
enzymes such as DNases, which begin to cleave the DNA in
the nucleus.
Importance of Apoptosis
1) Crucial for embryonic development
-Errors in Apoptosis can lead to Birth Defects
2) Important for maintaining homeostasis
- Cell death is balanced with mitosis to regulate cell number.
3) Improper regulation contributes to human disease
- Neurodegenerative diseases
Parkinson’s
Alzheimer’s
- Cancer
- Autoimmune diseases e.g. (diabetes type I)
- Viral diseases
Characteristics
• It is a process that occurs in almost all living
creatures since their early stages of embryological
development.
• It is an active cytological process in which energy
is consumed (ATP dependent)
• It is programmed or controlled by genetic protocol
or program (control of enzymes, cell membrane
surface proteins & cytoplasmic molecules, signal
transduction, gene expression)
• It may be triggered by intrinsic or extrinsic stimuli
Morphology
• Cell shrinkage (condensation of cytoplasm)
• Breakdown of mitochondria; release of
cytochrome C
• Nuclear condensation
• Nuclear fragmentation
• Cell membrane blebbing
• Fragmentation; apoptotic body formation:
membrane-bound cellular fragments, which often
lack nuclei
• Phagocytosis
Cellular changes associated with apoptosis
How Apoptosis Differs from Necrosis?
1.
2.
3.
4.
5.
6.
7.
8.
Apoptosis is intrinsically controlled, necrosis is not
Apoptosis is more rapid (12-24 hours) than necrosis
Apoptosis is induced by endogenous or exogenous stimuli,
necrosis is always induced by exogenous harms
Apoptosis is limited to single or few cells at a time, and
occurs among healthy cell population, necrosis is usually
more extensive & occurs in tissue exposed to injuries
Cell cytoplasm shrinks in apoptosis and swells in necrosis.
Nucleosomes of apoptotic cells are 180 bp fragments,
contrary to the irregular ones in necrosis
Apoptosis has no inflammation, while necrosis leads to
liberation of pro-inflammatory mediators
Apoptosis has no systemic manifestations contrary to most
inflammations
Mechanism
I. Four stages of apoptosis have been defined:
i. Committment to death by extracellular or
intracellular triggers/signals
ii. Cell killing (execution) by activation of
intracellular proteases (caspases)
iii. Engulfment of cell corpse by other cells
iv. Degradation of the cell corpse within the
lysosomes of phagocytic cells
II. Stimuli for Apoptotic Cell Death in Mammals
i. Growth factor deficiencies
ii. Ionizing radiation/ viral infection
iii. Free radical toxicity
iv. Death receptor activation (such as Fas or
CD95 triggering)
v. Metabolic or cell cycle perturbation
Stimuli for Apoptotic Cell Death
Death Factors
Definition: cytokines that activate an apoptosis
program by binding to their specific
receptor. Typical examples of death factors
are:
1. Fas ligand,
2. TNF (tumor necrosis factor) and
3. TRAIL (TNF-related apoptosis-inducing
ligand).
- Apoptosis can also be induced by cytotoxic Tlymphocytes using the enzyme granzyme.
III. Activation of Caspase cascade
i. Various stimuli described above eventually
activate the executioner (caspase) cascade
ii. At least 14 different caspases exist in human
cells
iii. Caspase cascades are apparently required for
complete execution
40
The extrinsic (death receptor-initiated) pathway of apoptosis, illustrated
by the events following Fas engagement. FADD= Fas associated death
domain.
Caspases are central initiators and executioners of apoptosis
• The
term caspases is derived from cysteinedependent aspartate-specific proteases: their
catalytical activity depends on a critical cysteineresidue within a highly conserved active-site
pentapeptide QACRG, and the caspases specifically
cleave their substrates after Asp residues.
• Initiator caspases include: 2, 8, 9, 10
• Execution caspases include: 3, 6, 7