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INTRODUCTION TO
STEM CELLS
STEM CELLS: A revolutionary idea in
medicine
Today’s medicine tries to support or treat
injured tissues and organs
but
Stem cells might simply REPLACE damaged cells or
possibly even REGENERATE damaged tissues.
Instead of transplanting organs, we
could rebuild and restore the tissue!
WHAT ARE STEM CELLS?
Stem cell is a special kind of cell that has a
unique capacity to renew itself and give rise to
specialized cell types.
It is uncommitted and remains uncommitted until
it receives a signal to develop into a specialized
cell.
 self-replicating, unspecialized cells
 capable of generating specialized daughter cell progeny
 plentiful in early embryonic development
 capacity for self-renewal decreases with aging
 categorized as embryonic or adult varieties
 possess specific markers enabling identification and lineage
 exhibit varying “plasticity” depending upon environment and
commitment level
WHAT ARE PROGENITOR
CELLS?
A progenitor/ precursor cell occurs in fetal or adult tissues and is
partially specialized, it divides and gives rise to differentiated cells.
Difference b/w PROGENITOR AND STEM CELL
Stem Cell
Specialized Cell e.g.
neuron, muscle etc
STEM CELL
Progenitor
cell
Specialized Cell e.g.
neuron, muscle etc
Specialized Cell e.g.
neuron, muscle etc
Totipotent: capable of any fate,
generating all cell types necessary for the
organism
Pluripotent: possible cell
types more restricted, cannot
make all tissues required for development
Multipotent: limited to a low number
of specialized cell types in differentiated
tissues
Stages of commitment: low to high
SYMMETRIC DIVISION
During early embryonic development, each cell divides and give rise
to two daughter cells with the same potential which are totipotent
ASYMMETRIC DIVISION
In adults each progenitor cell divides to form one progenitor daughter cell
and one daughter cell that begins the process of differentiation
Progenitor cell
Differentiated cell
ORIGIN OF STEM CELLS
Zygote Totipotent (has potential to form
whole organism)
Morula compact ball of cells
Blastocyst Outer layer trophoblast and
inner cell mass
Inner Cell Mass Pluripotent (stem cells that can give
rise to cells derived from all three
embryonic germ layers – mesoderm,
endoderm and ectoderm
30hrs after
fertilization
5-6 days after
fertilization
TYPES OF STEM CELLS
There are mainly three types of stem cells
EMBRYONIC STEM CELLS
An embryonic stem-cell is derived from a group of cells called inner cell mass
(ICM) which is part of the early (4-5 day) embryo called the blastocyst.
EMBRYONIC GERM CELLS
An embryonic germ-cell (EGC) is derived from the primordial germ cells of
the gonadal ridge of the 5-10 week fetus.
ADULT DERIVED STEM CELLS
An adult stem-cell is an undifferentiated cell that occurs in a differentiated
tissue, and becomes specialized to yield all of the specialized cell types of
the tissue from which it originated.
Sources of adult stem-cells include bone marrow, blood, the cornea and the
retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining of
the gastrointestinal track, heart, Inner ear and pancreas.
DISTINGUISHING FEATURE
Embryonic Stem Cells
• Inner Cell Mass
• Unlimited number of symmetrical
divisions without differentiation (for 2
years)
• Pluripotent (capacity variable) plasticity
unlimited
• Teratoma production when injected in
mouse.
• Expression of the transcription factor
OCT4
• Express a set of specific markers
• Active Telomerase
Embryonic Germ Cells
• Primordial Germ Cells, Gonadal
ridge of the 5-10 week fetus
• Moderate number of symmetrical
division without differentiation 70-
80 population doubling
• Pluripotent (capacity variable)
plasticity unlimited
• No teratoma production.
• Expression of the transcription
factor OCT4
• Express a set of specific markers
• Active Telomerase
• Adult organs.
• A limited number of divisions
• Mono or di – or may be tri-
potent (limited plasticity)
• No teratoma production.
• Expression of the transcription
factor OCT4
• Express a set of specific marker
• Active Telomerase
* Bone marrow, blood, the cornea and retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining
of the gastrointestinal track, and pancreas.
*
Adult Stem Cells
PROPERTIES OF STEM CELLS
1. CLONALITY
Cell is clonally derived or exhibits clonality if it was
generated by the division of a single cell and is
genetically identical to the parent.
2. PLURIPOTENCY
Cells capable of generating different cell types
originated from three germ layers, ecto, endo and
mesoderm
3.PLASTICITY
Plasticity of adult stem allows
them to develop into varied
paths of differentiation that
would not be expected based
upon their origin.
Thus, the fate of adult stem
cells depends upon their
environment, although the
efficiency of
transdifferentiation remains
an issue.
IDENTIFICATION OF STEM CELL
SURFACE MARKERS
EARLY TRANSCRIPTION FACTORS
TECHNIQUES INVOLVED
Magnetic Activated Cell Sorting (MACS)
Fluorescence Activated Cell Sorting (FACS)
IMMUNOCYTO-HISTOCHEMISTRY USING CELL SURFACE
MARKERS
Stem Cell and Microenvironment
STEM CELL NICHES: the stem cell incubator
Niches: house stem cells,
controlling their self—renewal
and progeny production in-vivo.
These microenvironments are
incubators to protect and serve
their resident stem cell
population.
HOW HAVE STEM CELLS BEEN USED?
STEM CELLS AND BLOOD
STEM CELLS AND NERVOUS SYSTEM
Neural stem cells have been identified in the adult brain.
Stem cells can acquire characteristics of neurons as well
supporting cells (astrocytes and oligodendroglia).
Stem cells improve movement in paralyzed mice.
Clinical trials with Parkinson’s disease patients showed
promising results, likely to improve with more research.
Stem cells and diabetes
Current research focuses upon adult stem cells that may
be precursors to islet cells and cells that produce insulin.
More recent studies in mice show embryonic stem cells
can differentiate into insulin-producing beta cells.
STEM CELLS AND SKIN
STEM CELL AND HEART
GENETICALLY MODIFIED STEM CELLS
Viral vectors used to alter the genetic
makeup of stem cells allows introduction
of new genes.
Genetically modified stem cells can be
used as a delivery vehicle and can be
utilized in correction of several disorders
such as induced pluripotent stem cells.
LIMITATIONS OF STEM CELL BIOLOGY
Concerns for stem cell biology
Safety concerns: production of teratomas
Ethical concerns
Immunologic Compatibilities
Careful clinical trials
Instead of all limitations and concerns, stem cell biology
is a promising field, opening up a new avenue in the field
of medicine but still a lot more is to be determined before
curing patients
https://youtu.be/S8nPXh3B3X0

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Lect 1- INTRODUCTION TO STEM CELLS.ppt

  • 2. STEM CELLS: A revolutionary idea in medicine Today’s medicine tries to support or treat injured tissues and organs but Stem cells might simply REPLACE damaged cells or possibly even REGENERATE damaged tissues. Instead of transplanting organs, we could rebuild and restore the tissue!
  • 3. WHAT ARE STEM CELLS? Stem cell is a special kind of cell that has a unique capacity to renew itself and give rise to specialized cell types. It is uncommitted and remains uncommitted until it receives a signal to develop into a specialized cell.
  • 4.  self-replicating, unspecialized cells  capable of generating specialized daughter cell progeny  plentiful in early embryonic development  capacity for self-renewal decreases with aging  categorized as embryonic or adult varieties  possess specific markers enabling identification and lineage  exhibit varying “plasticity” depending upon environment and commitment level
  • 5. WHAT ARE PROGENITOR CELLS? A progenitor/ precursor cell occurs in fetal or adult tissues and is partially specialized, it divides and gives rise to differentiated cells. Difference b/w PROGENITOR AND STEM CELL Stem Cell Specialized Cell e.g. neuron, muscle etc STEM CELL Progenitor cell Specialized Cell e.g. neuron, muscle etc Specialized Cell e.g. neuron, muscle etc
  • 6. Totipotent: capable of any fate, generating all cell types necessary for the organism Pluripotent: possible cell types more restricted, cannot make all tissues required for development Multipotent: limited to a low number of specialized cell types in differentiated tissues Stages of commitment: low to high
  • 7.
  • 8.
  • 9.
  • 10. SYMMETRIC DIVISION During early embryonic development, each cell divides and give rise to two daughter cells with the same potential which are totipotent ASYMMETRIC DIVISION In adults each progenitor cell divides to form one progenitor daughter cell and one daughter cell that begins the process of differentiation Progenitor cell Differentiated cell
  • 11. ORIGIN OF STEM CELLS Zygote Totipotent (has potential to form whole organism) Morula compact ball of cells Blastocyst Outer layer trophoblast and inner cell mass Inner Cell Mass Pluripotent (stem cells that can give rise to cells derived from all three embryonic germ layers – mesoderm, endoderm and ectoderm 30hrs after fertilization 5-6 days after fertilization
  • 12.
  • 13. TYPES OF STEM CELLS There are mainly three types of stem cells EMBRYONIC STEM CELLS An embryonic stem-cell is derived from a group of cells called inner cell mass (ICM) which is part of the early (4-5 day) embryo called the blastocyst. EMBRYONIC GERM CELLS An embryonic germ-cell (EGC) is derived from the primordial germ cells of the gonadal ridge of the 5-10 week fetus. ADULT DERIVED STEM CELLS An adult stem-cell is an undifferentiated cell that occurs in a differentiated tissue, and becomes specialized to yield all of the specialized cell types of the tissue from which it originated. Sources of adult stem-cells include bone marrow, blood, the cornea and the retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining of the gastrointestinal track, heart, Inner ear and pancreas.
  • 14. DISTINGUISHING FEATURE Embryonic Stem Cells • Inner Cell Mass • Unlimited number of symmetrical divisions without differentiation (for 2 years) • Pluripotent (capacity variable) plasticity unlimited • Teratoma production when injected in mouse. • Expression of the transcription factor OCT4 • Express a set of specific markers • Active Telomerase Embryonic Germ Cells • Primordial Germ Cells, Gonadal ridge of the 5-10 week fetus • Moderate number of symmetrical division without differentiation 70- 80 population doubling • Pluripotent (capacity variable) plasticity unlimited • No teratoma production. • Expression of the transcription factor OCT4 • Express a set of specific markers • Active Telomerase • Adult organs. • A limited number of divisions • Mono or di – or may be tri- potent (limited plasticity) • No teratoma production. • Expression of the transcription factor OCT4 • Express a set of specific marker • Active Telomerase * Bone marrow, blood, the cornea and retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining of the gastrointestinal track, and pancreas. * Adult Stem Cells
  • 15. PROPERTIES OF STEM CELLS 1. CLONALITY Cell is clonally derived or exhibits clonality if it was generated by the division of a single cell and is genetically identical to the parent. 2. PLURIPOTENCY Cells capable of generating different cell types originated from three germ layers, ecto, endo and mesoderm
  • 16. 3.PLASTICITY Plasticity of adult stem allows them to develop into varied paths of differentiation that would not be expected based upon their origin. Thus, the fate of adult stem cells depends upon their environment, although the efficiency of transdifferentiation remains an issue.
  • 17. IDENTIFICATION OF STEM CELL SURFACE MARKERS EARLY TRANSCRIPTION FACTORS TECHNIQUES INVOLVED Magnetic Activated Cell Sorting (MACS) Fluorescence Activated Cell Sorting (FACS) IMMUNOCYTO-HISTOCHEMISTRY USING CELL SURFACE MARKERS
  • 18. Stem Cell and Microenvironment
  • 19. STEM CELL NICHES: the stem cell incubator Niches: house stem cells, controlling their self—renewal and progeny production in-vivo. These microenvironments are incubators to protect and serve their resident stem cell population.
  • 20. HOW HAVE STEM CELLS BEEN USED? STEM CELLS AND BLOOD
  • 21. STEM CELLS AND NERVOUS SYSTEM Neural stem cells have been identified in the adult brain. Stem cells can acquire characteristics of neurons as well supporting cells (astrocytes and oligodendroglia). Stem cells improve movement in paralyzed mice. Clinical trials with Parkinson’s disease patients showed promising results, likely to improve with more research.
  • 22. Stem cells and diabetes Current research focuses upon adult stem cells that may be precursors to islet cells and cells that produce insulin. More recent studies in mice show embryonic stem cells can differentiate into insulin-producing beta cells.
  • 23.
  • 25. STEM CELL AND HEART
  • 26. GENETICALLY MODIFIED STEM CELLS Viral vectors used to alter the genetic makeup of stem cells allows introduction of new genes. Genetically modified stem cells can be used as a delivery vehicle and can be utilized in correction of several disorders such as induced pluripotent stem cells.
  • 27. LIMITATIONS OF STEM CELL BIOLOGY
  • 28. Concerns for stem cell biology Safety concerns: production of teratomas Ethical concerns Immunologic Compatibilities Careful clinical trials Instead of all limitations and concerns, stem cell biology is a promising field, opening up a new avenue in the field of medicine but still a lot more is to be determined before curing patients