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Topic: Advances In Stem CellTopic: Advances In Stem Cell
ResearchResearch
Submitted By: M.Z.Arifeen.Submitted By: M.Z.Arifeen.
Submitted To: Dr. Aftab Ali ShahSubmitted To: Dr. Aftab Ali Shah
Student Of: M.Phil in BiotecnologyStudent Of: M.Phil in Biotecnology
University of MalakandUniversity of Malakand
11
INTRODUCTION OF STEMINTRODUCTION OF STEM
CELL TECHNOLOGYCELL TECHNOLOGY
Stem Cell – DefinitionStem Cell – Definition
• A cell that has the ability toA cell that has the ability to
continuously divide and differentiatecontinuously divide and differentiate
(develop) into various other kind(s) of(develop) into various other kind(s) of
cells/tissuescells/tissues
33
Stem Cell CharacteristicsStem Cell Characteristics
 ‘‘Blank cells’ (unspecialized)Blank cells’ (unspecialized)
 Capable of dividing and renewingCapable of dividing and renewing
themselves for long periods of timethemselves for long periods of time
(proliferation and renewal)(proliferation and renewal)
 Have the potential to give rise toHave the potential to give rise to
specialized cell types (differentiation)specialized cell types (differentiation)
44
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Kinds of Stem CellsKinds of Stem Cells
Stem cellStem cell
typetype DescriptionDescription ExamplesExamples
TotipotentTotipotent
Each cell can developEach cell can develop
into a new individualinto a new individual
Cells from early (1-Cells from early (1-
3 days) embryos3 days) embryos
PluripotentPluripotent
Cells can form any (overCells can form any (over
200) cell types200) cell types
Some cells ofSome cells of
blastocyst (5 to 14blastocyst (5 to 14
days)days)
MultipotentMultipotent
Cells differentiated, butCells differentiated, but
can form a number ofcan form a number of
other tissuesother tissues cells can
differentiate into a number of
cells, but only those of a closely
related family of cells
Fetal tissue, cordFetal tissue, cord
blood, and adultblood, and adult
stem cellsstem cells
66
OligopotentOligopotent: stem cells can differentiate into only a few: stem cells can differentiate into only a few
cells, such as lymphoid or myeloid stem cellscells, such as lymphoid or myeloid stem cells
UnipotentUnipotent cells can produce only one cell type, theircells can produce only one cell type, their
own,own, but have the property of self-renewal, whichbut have the property of self-renewal, which
distinguishes them from non-stem cells (e.g., muscledistinguishes them from non-stem cells (e.g., muscle
stem cells).stem cells).
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Stem Cell DifferentiationStem Cell Differentiation
Princeton University
88
This cellThis cell
Can form theCan form the
Embryo and placentaEmbryo and placenta
This cellThis cell
Can just form theCan just form the
embryoembryo
Fully matureFully mature 99
Kinds of Stem CellsKinds of Stem Cells
Embryonic stem cells come from a five to six-day-old embryo. They
have the ability to form virtually any type of cell found in the human
body.
Embryonic germ cells are derived from the part of a human embryo or
foetus that will ultimately produce eggs or sperm (gametes).
Adult stem cells are undifferentiated cells found among specialised or
differentiated cells in a tissue or organ after birth. Based on current
research they appear to have a more restricted ability to produce
different cell types and to self-renew.
1010
1111
Blastocyst DiagramBlastocyst Diagram
Princeton University
1212
Sexual ReproductionSexual Reproduction
The Association of Reproductive Health Professionals
1313
Stages of EmbryogenesisStages of Embryogenesis
Day 1
Fertilized egg
Day 2
2-cell embryo Day 3-4
Multi-cell embryo
Day 5-6
BlastocystDay 11-14
Tissue Differentiation 1414
Derivation and Use ofDerivation and Use of
Embryonic Stem Cell LinesEmbryonic Stem Cell Lines
Isolate inner cell mass
(destroys embryo)
Heart muscleKidney
“Special sauce”
(largely unknown)
Day 5-6
Blastocyst
Inner cells
(forms fetus)
Outer cells
(forms placenta)
Heart
repaired
Culture cells
1515
Stages of EmbryogenesisStages of Embryogenesis
blastocystblastocyst Blastocyst inner mass cellsBlastocyst inner mass cells
8-cell stage8-cell stagecleavagecleavage
1616
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An adult stem cell is thought to be anAn adult stem cell is thought to be an undifferentiatedundifferentiated cell,cell,
found among differentiated cells in a tissue or organ that can renewfound among differentiated cells in a tissue or organ that can renew
itself and can differentiate to yield some or all of the majoritself and can differentiate to yield some or all of the major
specialized cell types of the tissue or organ.specialized cell types of the tissue or organ.
The primary roles ofThe primary roles of adult stem cellsadult stem cells in a living organism are toin a living organism are to
maintain and repair the tissue in which they are found.maintain and repair the tissue in which they are found.
Scientists also use the termScientists also use the term somatic stem cellsomatic stem cell instead of adultinstead of adult
stem cell, where somatic refers to cells of the body (not the germstem cell, where somatic refers to cells of the body (not the germ
cells, sperm or eggs).cells, sperm or eggs).
What are adult stem cells?What are adult stem cells?
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If the differentiation of adult stem cells can be controlled in theIf the differentiation of adult stem cells can be controlled in the
laboratory, these cells may become the basis of transplantation-laboratory, these cells may become the basis of transplantation-
based therapies.based therapies.
The history of research on adult stem cells began about 60 yearsThe history of research on adult stem cells began about 60 years
ago. In the 1950s, researchers discovered that the bone marrowago. In the 1950s, researchers discovered that the bone marrow
contains at least two kinds of stem cells.contains at least two kinds of stem cells.
1.1.One population, calledOne population, called hematopoietic stem cellshematopoietic stem cells, forms all the, forms all the
types of blood cells in the body.types of blood cells in the body.
2.2.A second population, calledA second population, called bone marrow stromal stembone marrow stromal stem
cellscells (skeletal stem cells), These non-hematopoietic stem cells(skeletal stem cells), These non-hematopoietic stem cells
make up a small proportion of themake up a small proportion of the stromal cellstromal cell population in thepopulation in the
bone marrow, and can generate bone, cartilage, fat, cells thatbone marrow, and can generate bone, cartilage, fat, cells that
support the formation of blood, and fibrous connective tissue.support the formation of blood, and fibrous connective tissue.
2020
Where are adult stem cells found, andWhere are adult stem cells found, and
what do they normally do?what do they normally do?
Adult stem cells have been identified in many organs and tissues,Adult stem cells have been identified in many organs and tissues,
including brain, bone marrow, peripheral blood, blood vessels,including brain, bone marrow, peripheral blood, blood vessels,
skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium,skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium,
and testis.and testis.
They are thought to reside in a specific area of each tissueThey are thought to reside in a specific area of each tissue
called a "stem cell niche.called a "stem cell niche.
Stem cells remain non-dividing for long periods of time untilStem cells remain non-dividing for long periods of time until
they are activated by a normal need for more cells to maintainthey are activated by a normal need for more cells to maintain
tissues, or by disease or tissue injury.tissues, or by disease or tissue injury.
2121
Typically, there is a very small number of stem cells in eachTypically, there is a very small number of stem cells in each
tissue, and once removed from the body, their capacity to divide istissue, and once removed from the body, their capacity to divide is
limited, making generation of large quantities of stem cellslimited, making generation of large quantities of stem cells
difficult.difficult.
Scientists in many laboratories are trying to find better ways toScientists in many laboratories are trying to find better ways to
grow large quantities of adult stem cells ingrow large quantities of adult stem cells in cell culturecell culture and toand to
manipulate them to generate specific cell types so they can be usedmanipulate them to generate specific cell types so they can be used
to treat injury or disease.to treat injury or disease.
Some examples of potential treatments include regeneratingSome examples of potential treatments include regenerating
bone using cells derived from bone marrow stroma, developingbone using cells derived from bone marrow stroma, developing
insulin-producing cells for type 1 diabetes, and repairing damagedinsulin-producing cells for type 1 diabetes, and repairing damaged
heart muscle following a heart attack with cardiac muscle cells.heart muscle following a heart attack with cardiac muscle cells.
2222
AdultAdult stemstem cellscells
2323
2424
scientists have reported that adult stem cells occur in manyscientists have reported that adult stem cells occur in many
tissues and that they enter normaltissues and that they enter normal differentiationdifferentiation pathways topathways to
form the specialized cell types of the tissue in which they reside.form the specialized cell types of the tissue in which they reside.
Normal differentiation pathways of adult stem cells:Normal differentiation pathways of adult stem cells:
In a living animal, adult stem cells are available to divide,In a living animal, adult stem cells are available to divide,
when needed, and can give rise to mature cell types that havewhen needed, and can give rise to mature cell types that have
characteristic shapes and specialized structures and functions ofcharacteristic shapes and specialized structures and functions of
a particular tissue.a particular tissue.
The following are examples of differentiation pathways ofThe following are examples of differentiation pathways of
adult stem cells that have been demonstratedadult stem cells that have been demonstrated in vitroin vitro oror in vivoin vivo..
2525
Hematopoietic stem cells give rise to all the types of blood cells:Hematopoietic stem cells give rise to all the types of blood cells:
red blood cells, B lymphocytes, T lymphocytes, natural killerred blood cells, B lymphocytes, T lymphocytes, natural killer
cells, neutrophils, basophils, eosinophils, monocytes, andcells, neutrophils, basophils, eosinophils, monocytes, and
macrophages.macrophages.
Mesenchymal stem cellsMesenchymal stem cells give rise to a variety of cell types:give rise to a variety of cell types:
bone cells (osteocytes), cartilage cells (chondrocytes), fat cellsbone cells (osteocytes), cartilage cells (chondrocytes), fat cells
(adipocytes), and other kinds of connective tissue cells such as(adipocytes), and other kinds of connective tissue cells such as
those in tendons.those in tendons.
Neural stem cellsNeural stem cells in the brain give rise to its three major cellin the brain give rise to its three major cell
types: nerve cells (neurons) and two categories of non-neuronaltypes: nerve cells (neurons) and two categories of non-neuronal
cells—astrocytes and oligodendrocytes.cells—astrocytes and oligodendrocytes.
2626
Epithelial stem cellsEpithelial stem cells in the lining of the digestive tractin the lining of the digestive tract
occur in deep crypts and give rise to several cell types:occur in deep crypts and give rise to several cell types:
absorptive cells, goblet cells, paneth cells, and enteroendocrineabsorptive cells, goblet cells, paneth cells, and enteroendocrine
cells.cells.
Skin stem cellsSkin stem cells occur in the basal layer of the epidermis andoccur in the basal layer of the epidermis and
at the base of hair follicles. The epidermal stem cells give rise toat the base of hair follicles. The epidermal stem cells give rise to
keratinocytes, which migrate to the surface of the skin and formkeratinocytes, which migrate to the surface of the skin and form
a protective layer. The follicular stem cells can give rise to botha protective layer. The follicular stem cells can give rise to both
the hair follicle and to the epidermis.the hair follicle and to the epidermis.
2727
2828
2929
The Promise of Stem CellsThe Promise of Stem Cells
potential application of stem cells is making cells and tissues forpotential application of stem cells is making cells and tissues for
medical therapiesmedical therapies
Today, donated organs and tissues are often used to replaceToday, donated organs and tissues are often used to replace
those that are diseased or destroyedthose that are diseased or destroyed
Unfortunately, the number of people needing a transplant farUnfortunately, the number of people needing a transplant far
exceeds the number of organs available for transplantationexceeds the number of organs available for transplantation
Pluripotent stem cells offer the possibility of a renewablePluripotent stem cells offer the possibility of a renewable
source of replacement cells and tissues to treat diseases,source of replacement cells and tissues to treat diseases,
conditions, and disabilities including Parkinson's disease,conditions, and disabilities including Parkinson's disease,
amyotrophic lateral sclerosis, spinal cord injury, burns, heartamyotrophic lateral sclerosis, spinal cord injury, burns, heart
disease, diabetes, and arthritis.disease, diabetes, and arthritis.
3030
ApplicationsApplications
 Disease
• Diabetes, Spinal
cord injury,
Parkinson’s
disease, heart
disease
 Genetic based
Disease
• Cystic fibrosis,
Huntington’s
3131
3232
Somatic Stem Cell Therapy: Using a Bone MarrowSomatic Stem Cell Therapy: Using a Bone Marrow
Transplant to Cure LeukemiaTransplant to Cure Leukemia
Leukemia is a cancer of white blood cells, or leukocytes.Leukemia is a cancer of white blood cells, or leukocytes.
Like other blood cells, leukocytes develop from somatic stemLike other blood cells, leukocytes develop from somatic stem
cells. Mature leukocytes are released into the bloodstream, wherecells. Mature leukocytes are released into the bloodstream, where
they work to fight off infections in our bodies.they work to fight off infections in our bodies.
Leukemia results when leukocytes begin to grow and functionLeukemia results when leukocytes begin to grow and function
abnormally, becoming cancerousabnormally, becoming cancerous
Successful treatment for leukemia depends on getting rid of allSuccessful treatment for leukemia depends on getting rid of all
the abnormal leukocytes in the patient, allowing healthy ones tothe abnormal leukocytes in the patient, allowing healthy ones to
grow in their place. One way to do this is through chemotherapy,grow in their place. One way to do this is through chemotherapy,
which uses potent drugs to target and kill the abnormal cells.which uses potent drugs to target and kill the abnormal cells.
When chemotherapy alone can't eliminate them all, physiciansWhen chemotherapy alone can't eliminate them all, physicians
sometimes turn to bone marrow transplants.sometimes turn to bone marrow transplants.
3333
In a bone marrow transplant, the patient's bone marrow stem cellsIn a bone marrow transplant, the patient's bone marrow stem cells
are replaced with those from a healthy, matching donorare replaced with those from a healthy, matching donor
To do this, all of the patient's existing bone marrow andTo do this, all of the patient's existing bone marrow and
abnormal leukocytes are first killed using a combination ofabnormal leukocytes are first killed using a combination of
chemotherapy and radiation.chemotherapy and radiation.
Next, a sample of donor bone marrow containing healthy stemNext, a sample of donor bone marrow containing healthy stem
cells is introduced into the patient's bloodstream.cells is introduced into the patient's bloodstream.
If the transplant is successful, the stem cells will migrate intoIf the transplant is successful, the stem cells will migrate into
the patient's bone marrow and begin producing new, healthythe patient's bone marrow and begin producing new, healthy
leukocytes to replace the abnormal cells.leukocytes to replace the abnormal cells.
3434
3535
Umbilical Cord Blood Stem CellsUmbilical Cord Blood Stem Cells
Newborn infants no longer need their umbilical cords, so theyNewborn infants no longer need their umbilical cords, so they
have traditionally been discarded as a by-product of the birthhave traditionally been discarded as a by-product of the birth
process. In recent years, however, the stem-cell–rich blood foundprocess. In recent years, however, the stem-cell–rich blood found
in the umbilical cord has proven useful in treating the same typesin the umbilical cord has proven useful in treating the same types
of health problems as those treated using bone marrow stem cellsof health problems as those treated using bone marrow stem cells
and PBSCs.and PBSCs.
Umbilical cord blood stem cell transplants are less prone toUmbilical cord blood stem cell transplants are less prone to
rejection than either bone marrow or peripheral blood stem cells.rejection than either bone marrow or peripheral blood stem cells.
This is probably because the cells have not yet developed theThis is probably because the cells have not yet developed the
features that can be recognized and attacked by the recipient'sfeatures that can be recognized and attacked by the recipient's
immune system. Also, because umbilical cord blood lacks well-immune system. Also, because umbilical cord blood lacks well-
developed immune cells, there is less chance that the transplanteddeveloped immune cells, there is less chance that the transplanted
cells will attack the recipient's body,cells will attack the recipient's body,
3636
3737
3838
3939
4040
4141
4242
4343
4444
4545
Unknowns in StemUnknowns in Stem
Cell/Cloning ResearchCell/Cloning Research
• It is uncertain that humanIt is uncertain that human
embryonic stem cellsembryonic stem cells in vitroin vitro cancan
give rise to all the different cellgive rise to all the different cell
types of the adult body.types of the adult body.
• It is unknown if stem cellsIt is unknown if stem cells
culturedcultured in vitroin vitro (apart from the(apart from the
embryo) will function as the cellsembryo) will function as the cells
do when they are part of thedo when they are part of the
developing embryodeveloping embryo
4646
Challenges to StemChallenges to Stem
Cell/Cloning ResearchCell/Cloning Research
• Stem cells need to beStem cells need to be
differentiated to thedifferentiated to the
appropriate cell type(s)appropriate cell type(s)
beforebefore they can be usedthey can be used
clinically.clinically.
• Recently, abnormalities inRecently, abnormalities in
chromosome number andchromosome number and
structure were found instructure were found in
three human ESC lines.three human ESC lines.
4747
Challenges to StemChallenges to Stem
Cell/Cloning ResearchCell/Cloning Research
• Stem cell development or proliferationStem cell development or proliferation
must be controlled once placed intomust be controlled once placed into
patients.patients.
• Possibility of rejection of stem cellPossibility of rejection of stem cell
transplants as foreign tissues is very high.transplants as foreign tissues is very high.
4848
Challenges to StemChallenges to Stem
Cell/Cloning ResearchCell/Cloning Research
• Contamination by viruses, bacteria, fungi,Contamination by viruses, bacteria, fungi,
and Mycoplasma possible.and Mycoplasma possible.
• The use of mouse “feeder” cells to growThe use of mouse “feeder” cells to grow
ESC could result in problems due toESC could result in problems due to
xenotransplantation (complicating FDAxenotransplantation (complicating FDA
requirements for clinical use).requirements for clinical use).
4949
(Time 2.19.01)
ThanksThanks
5050
In case of anyIn case of any
question pleasequestion please
contact me atcontact me at
zain_bbt@yahoo.comzain_bbt@yahoo.com

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Stem cell research

  • 1. Topic: Advances In Stem CellTopic: Advances In Stem Cell ResearchResearch Submitted By: M.Z.Arifeen.Submitted By: M.Z.Arifeen. Submitted To: Dr. Aftab Ali ShahSubmitted To: Dr. Aftab Ali Shah Student Of: M.Phil in BiotecnologyStudent Of: M.Phil in Biotecnology University of MalakandUniversity of Malakand 11
  • 2. INTRODUCTION OF STEMINTRODUCTION OF STEM CELL TECHNOLOGYCELL TECHNOLOGY
  • 3. Stem Cell – DefinitionStem Cell – Definition • A cell that has the ability toA cell that has the ability to continuously divide and differentiatecontinuously divide and differentiate (develop) into various other kind(s) of(develop) into various other kind(s) of cells/tissuescells/tissues 33
  • 4. Stem Cell CharacteristicsStem Cell Characteristics  ‘‘Blank cells’ (unspecialized)Blank cells’ (unspecialized)  Capable of dividing and renewingCapable of dividing and renewing themselves for long periods of timethemselves for long periods of time (proliferation and renewal)(proliferation and renewal)  Have the potential to give rise toHave the potential to give rise to specialized cell types (differentiation)specialized cell types (differentiation) 44
  • 5. 55
  • 6. Kinds of Stem CellsKinds of Stem Cells Stem cellStem cell typetype DescriptionDescription ExamplesExamples TotipotentTotipotent Each cell can developEach cell can develop into a new individualinto a new individual Cells from early (1-Cells from early (1- 3 days) embryos3 days) embryos PluripotentPluripotent Cells can form any (overCells can form any (over 200) cell types200) cell types Some cells ofSome cells of blastocyst (5 to 14blastocyst (5 to 14 days)days) MultipotentMultipotent Cells differentiated, butCells differentiated, but can form a number ofcan form a number of other tissuesother tissues cells can differentiate into a number of cells, but only those of a closely related family of cells Fetal tissue, cordFetal tissue, cord blood, and adultblood, and adult stem cellsstem cells 66
  • 7. OligopotentOligopotent: stem cells can differentiate into only a few: stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cellscells, such as lymphoid or myeloid stem cells UnipotentUnipotent cells can produce only one cell type, theircells can produce only one cell type, their own,own, but have the property of self-renewal, whichbut have the property of self-renewal, which distinguishes them from non-stem cells (e.g., muscledistinguishes them from non-stem cells (e.g., muscle stem cells).stem cells). 77
  • 8. Stem Cell DifferentiationStem Cell Differentiation Princeton University 88
  • 9. This cellThis cell Can form theCan form the Embryo and placentaEmbryo and placenta This cellThis cell Can just form theCan just form the embryoembryo Fully matureFully mature 99
  • 10. Kinds of Stem CellsKinds of Stem Cells Embryonic stem cells come from a five to six-day-old embryo. They have the ability to form virtually any type of cell found in the human body. Embryonic germ cells are derived from the part of a human embryo or foetus that will ultimately produce eggs or sperm (gametes). Adult stem cells are undifferentiated cells found among specialised or differentiated cells in a tissue or organ after birth. Based on current research they appear to have a more restricted ability to produce different cell types and to self-renew. 1010
  • 11. 1111
  • 13. Sexual ReproductionSexual Reproduction The Association of Reproductive Health Professionals 1313
  • 14. Stages of EmbryogenesisStages of Embryogenesis Day 1 Fertilized egg Day 2 2-cell embryo Day 3-4 Multi-cell embryo Day 5-6 BlastocystDay 11-14 Tissue Differentiation 1414
  • 15. Derivation and Use ofDerivation and Use of Embryonic Stem Cell LinesEmbryonic Stem Cell Lines Isolate inner cell mass (destroys embryo) Heart muscleKidney “Special sauce” (largely unknown) Day 5-6 Blastocyst Inner cells (forms fetus) Outer cells (forms placenta) Heart repaired Culture cells 1515
  • 16. Stages of EmbryogenesisStages of Embryogenesis blastocystblastocyst Blastocyst inner mass cellsBlastocyst inner mass cells 8-cell stage8-cell stagecleavagecleavage 1616
  • 17. 1717
  • 18. 1818
  • 19. An adult stem cell is thought to be anAn adult stem cell is thought to be an undifferentiatedundifferentiated cell,cell, found among differentiated cells in a tissue or organ that can renewfound among differentiated cells in a tissue or organ that can renew itself and can differentiate to yield some or all of the majoritself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ.specialized cell types of the tissue or organ. The primary roles ofThe primary roles of adult stem cellsadult stem cells in a living organism are toin a living organism are to maintain and repair the tissue in which they are found.maintain and repair the tissue in which they are found. Scientists also use the termScientists also use the term somatic stem cellsomatic stem cell instead of adultinstead of adult stem cell, where somatic refers to cells of the body (not the germstem cell, where somatic refers to cells of the body (not the germ cells, sperm or eggs).cells, sperm or eggs). What are adult stem cells?What are adult stem cells? 1919
  • 20. If the differentiation of adult stem cells can be controlled in theIf the differentiation of adult stem cells can be controlled in the laboratory, these cells may become the basis of transplantation-laboratory, these cells may become the basis of transplantation- based therapies.based therapies. The history of research on adult stem cells began about 60 yearsThe history of research on adult stem cells began about 60 years ago. In the 1950s, researchers discovered that the bone marrowago. In the 1950s, researchers discovered that the bone marrow contains at least two kinds of stem cells.contains at least two kinds of stem cells. 1.1.One population, calledOne population, called hematopoietic stem cellshematopoietic stem cells, forms all the, forms all the types of blood cells in the body.types of blood cells in the body. 2.2.A second population, calledA second population, called bone marrow stromal stembone marrow stromal stem cellscells (skeletal stem cells), These non-hematopoietic stem cells(skeletal stem cells), These non-hematopoietic stem cells make up a small proportion of themake up a small proportion of the stromal cellstromal cell population in thepopulation in the bone marrow, and can generate bone, cartilage, fat, cells thatbone marrow, and can generate bone, cartilage, fat, cells that support the formation of blood, and fibrous connective tissue.support the formation of blood, and fibrous connective tissue. 2020
  • 21. Where are adult stem cells found, andWhere are adult stem cells found, and what do they normally do?what do they normally do? Adult stem cells have been identified in many organs and tissues,Adult stem cells have been identified in many organs and tissues, including brain, bone marrow, peripheral blood, blood vessels,including brain, bone marrow, peripheral blood, blood vessels, skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium,skeletal muscle, skin, teeth, heart, gut, liver, ovarian epithelium, and testis.and testis. They are thought to reside in a specific area of each tissueThey are thought to reside in a specific area of each tissue called a "stem cell niche.called a "stem cell niche. Stem cells remain non-dividing for long periods of time untilStem cells remain non-dividing for long periods of time until they are activated by a normal need for more cells to maintainthey are activated by a normal need for more cells to maintain tissues, or by disease or tissue injury.tissues, or by disease or tissue injury. 2121
  • 22. Typically, there is a very small number of stem cells in eachTypically, there is a very small number of stem cells in each tissue, and once removed from the body, their capacity to divide istissue, and once removed from the body, their capacity to divide is limited, making generation of large quantities of stem cellslimited, making generation of large quantities of stem cells difficult.difficult. Scientists in many laboratories are trying to find better ways toScientists in many laboratories are trying to find better ways to grow large quantities of adult stem cells ingrow large quantities of adult stem cells in cell culturecell culture and toand to manipulate them to generate specific cell types so they can be usedmanipulate them to generate specific cell types so they can be used to treat injury or disease.to treat injury or disease. Some examples of potential treatments include regeneratingSome examples of potential treatments include regenerating bone using cells derived from bone marrow stroma, developingbone using cells derived from bone marrow stroma, developing insulin-producing cells for type 1 diabetes, and repairing damagedinsulin-producing cells for type 1 diabetes, and repairing damaged heart muscle following a heart attack with cardiac muscle cells.heart muscle following a heart attack with cardiac muscle cells. 2222
  • 24. 2424
  • 25. scientists have reported that adult stem cells occur in manyscientists have reported that adult stem cells occur in many tissues and that they enter normaltissues and that they enter normal differentiationdifferentiation pathways topathways to form the specialized cell types of the tissue in which they reside.form the specialized cell types of the tissue in which they reside. Normal differentiation pathways of adult stem cells:Normal differentiation pathways of adult stem cells: In a living animal, adult stem cells are available to divide,In a living animal, adult stem cells are available to divide, when needed, and can give rise to mature cell types that havewhen needed, and can give rise to mature cell types that have characteristic shapes and specialized structures and functions ofcharacteristic shapes and specialized structures and functions of a particular tissue.a particular tissue. The following are examples of differentiation pathways ofThe following are examples of differentiation pathways of adult stem cells that have been demonstratedadult stem cells that have been demonstrated in vitroin vitro oror in vivoin vivo.. 2525
  • 26. Hematopoietic stem cells give rise to all the types of blood cells:Hematopoietic stem cells give rise to all the types of blood cells: red blood cells, B lymphocytes, T lymphocytes, natural killerred blood cells, B lymphocytes, T lymphocytes, natural killer cells, neutrophils, basophils, eosinophils, monocytes, andcells, neutrophils, basophils, eosinophils, monocytes, and macrophages.macrophages. Mesenchymal stem cellsMesenchymal stem cells give rise to a variety of cell types:give rise to a variety of cell types: bone cells (osteocytes), cartilage cells (chondrocytes), fat cellsbone cells (osteocytes), cartilage cells (chondrocytes), fat cells (adipocytes), and other kinds of connective tissue cells such as(adipocytes), and other kinds of connective tissue cells such as those in tendons.those in tendons. Neural stem cellsNeural stem cells in the brain give rise to its three major cellin the brain give rise to its three major cell types: nerve cells (neurons) and two categories of non-neuronaltypes: nerve cells (neurons) and two categories of non-neuronal cells—astrocytes and oligodendrocytes.cells—astrocytes and oligodendrocytes. 2626
  • 27. Epithelial stem cellsEpithelial stem cells in the lining of the digestive tractin the lining of the digestive tract occur in deep crypts and give rise to several cell types:occur in deep crypts and give rise to several cell types: absorptive cells, goblet cells, paneth cells, and enteroendocrineabsorptive cells, goblet cells, paneth cells, and enteroendocrine cells.cells. Skin stem cellsSkin stem cells occur in the basal layer of the epidermis andoccur in the basal layer of the epidermis and at the base of hair follicles. The epidermal stem cells give rise toat the base of hair follicles. The epidermal stem cells give rise to keratinocytes, which migrate to the surface of the skin and formkeratinocytes, which migrate to the surface of the skin and form a protective layer. The follicular stem cells can give rise to botha protective layer. The follicular stem cells can give rise to both the hair follicle and to the epidermis.the hair follicle and to the epidermis. 2727
  • 28. 2828
  • 29. 2929
  • 30. The Promise of Stem CellsThe Promise of Stem Cells potential application of stem cells is making cells and tissues forpotential application of stem cells is making cells and tissues for medical therapiesmedical therapies Today, donated organs and tissues are often used to replaceToday, donated organs and tissues are often used to replace those that are diseased or destroyedthose that are diseased or destroyed Unfortunately, the number of people needing a transplant farUnfortunately, the number of people needing a transplant far exceeds the number of organs available for transplantationexceeds the number of organs available for transplantation Pluripotent stem cells offer the possibility of a renewablePluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat diseases,source of replacement cells and tissues to treat diseases, conditions, and disabilities including Parkinson's disease,conditions, and disabilities including Parkinson's disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heartamyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis.disease, diabetes, and arthritis. 3030
  • 31. ApplicationsApplications  Disease • Diabetes, Spinal cord injury, Parkinson’s disease, heart disease  Genetic based Disease • Cystic fibrosis, Huntington’s 3131
  • 32. 3232 Somatic Stem Cell Therapy: Using a Bone MarrowSomatic Stem Cell Therapy: Using a Bone Marrow Transplant to Cure LeukemiaTransplant to Cure Leukemia Leukemia is a cancer of white blood cells, or leukocytes.Leukemia is a cancer of white blood cells, or leukocytes. Like other blood cells, leukocytes develop from somatic stemLike other blood cells, leukocytes develop from somatic stem cells. Mature leukocytes are released into the bloodstream, wherecells. Mature leukocytes are released into the bloodstream, where they work to fight off infections in our bodies.they work to fight off infections in our bodies. Leukemia results when leukocytes begin to grow and functionLeukemia results when leukocytes begin to grow and function abnormally, becoming cancerousabnormally, becoming cancerous Successful treatment for leukemia depends on getting rid of allSuccessful treatment for leukemia depends on getting rid of all the abnormal leukocytes in the patient, allowing healthy ones tothe abnormal leukocytes in the patient, allowing healthy ones to grow in their place. One way to do this is through chemotherapy,grow in their place. One way to do this is through chemotherapy, which uses potent drugs to target and kill the abnormal cells.which uses potent drugs to target and kill the abnormal cells. When chemotherapy alone can't eliminate them all, physiciansWhen chemotherapy alone can't eliminate them all, physicians sometimes turn to bone marrow transplants.sometimes turn to bone marrow transplants.
  • 33. 3333 In a bone marrow transplant, the patient's bone marrow stem cellsIn a bone marrow transplant, the patient's bone marrow stem cells are replaced with those from a healthy, matching donorare replaced with those from a healthy, matching donor To do this, all of the patient's existing bone marrow andTo do this, all of the patient's existing bone marrow and abnormal leukocytes are first killed using a combination ofabnormal leukocytes are first killed using a combination of chemotherapy and radiation.chemotherapy and radiation. Next, a sample of donor bone marrow containing healthy stemNext, a sample of donor bone marrow containing healthy stem cells is introduced into the patient's bloodstream.cells is introduced into the patient's bloodstream. If the transplant is successful, the stem cells will migrate intoIf the transplant is successful, the stem cells will migrate into the patient's bone marrow and begin producing new, healthythe patient's bone marrow and begin producing new, healthy leukocytes to replace the abnormal cells.leukocytes to replace the abnormal cells.
  • 34. 3434
  • 35. 3535 Umbilical Cord Blood Stem CellsUmbilical Cord Blood Stem Cells Newborn infants no longer need their umbilical cords, so theyNewborn infants no longer need their umbilical cords, so they have traditionally been discarded as a by-product of the birthhave traditionally been discarded as a by-product of the birth process. In recent years, however, the stem-cell–rich blood foundprocess. In recent years, however, the stem-cell–rich blood found in the umbilical cord has proven useful in treating the same typesin the umbilical cord has proven useful in treating the same types of health problems as those treated using bone marrow stem cellsof health problems as those treated using bone marrow stem cells and PBSCs.and PBSCs. Umbilical cord blood stem cell transplants are less prone toUmbilical cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells.rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed theThis is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient'sfeatures that can be recognized and attacked by the recipient's immune system. Also, because umbilical cord blood lacks well-immune system. Also, because umbilical cord blood lacks well- developed immune cells, there is less chance that the transplanteddeveloped immune cells, there is less chance that the transplanted cells will attack the recipient's body,cells will attack the recipient's body,
  • 36. 3636
  • 37. 3737
  • 38. 3838
  • 39. 3939
  • 40. 4040
  • 41. 4141
  • 42. 4242
  • 43. 4343
  • 44. 4444
  • 45. 4545
  • 46. Unknowns in StemUnknowns in Stem Cell/Cloning ResearchCell/Cloning Research • It is uncertain that humanIt is uncertain that human embryonic stem cellsembryonic stem cells in vitroin vitro cancan give rise to all the different cellgive rise to all the different cell types of the adult body.types of the adult body. • It is unknown if stem cellsIt is unknown if stem cells culturedcultured in vitroin vitro (apart from the(apart from the embryo) will function as the cellsembryo) will function as the cells do when they are part of thedo when they are part of the developing embryodeveloping embryo 4646
  • 47. Challenges to StemChallenges to Stem Cell/Cloning ResearchCell/Cloning Research • Stem cells need to beStem cells need to be differentiated to thedifferentiated to the appropriate cell type(s)appropriate cell type(s) beforebefore they can be usedthey can be used clinically.clinically. • Recently, abnormalities inRecently, abnormalities in chromosome number andchromosome number and structure were found instructure were found in three human ESC lines.three human ESC lines. 4747
  • 48. Challenges to StemChallenges to Stem Cell/Cloning ResearchCell/Cloning Research • Stem cell development or proliferationStem cell development or proliferation must be controlled once placed intomust be controlled once placed into patients.patients. • Possibility of rejection of stem cellPossibility of rejection of stem cell transplants as foreign tissues is very high.transplants as foreign tissues is very high. 4848
  • 49. Challenges to StemChallenges to Stem Cell/Cloning ResearchCell/Cloning Research • Contamination by viruses, bacteria, fungi,Contamination by viruses, bacteria, fungi, and Mycoplasma possible.and Mycoplasma possible. • The use of mouse “feeder” cells to growThe use of mouse “feeder” cells to grow ESC could result in problems due toESC could result in problems due to xenotransplantation (complicating FDAxenotransplantation (complicating FDA requirements for clinical use).requirements for clinical use). 4949
  • 50. (Time 2.19.01) ThanksThanks 5050 In case of anyIn case of any question pleasequestion please contact me atcontact me at zain_bbt@yahoo.comzain_bbt@yahoo.com

Notas do Editor

  1. 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.
  2. Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
  3. Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
  4. Totipotent: These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent
  5. The lymphatic system is part of the circulatory system, comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph directionally towards the heart.
  6. Pluripotent, embryonic stem cells originate as inner cell mass (ICM) cells within a blastocyst. These stem cells can become any tissue in the body, excluding a placenta. Only cells from an earlier stage of the embryo, known as the morula, are totipotent, able to become all tissues in the body and the extraembryonic placenta.
  7. ES cell cultures have been grown for more than two years in the laboratory as immortal cell lines, but embryonic germ cellcultures can only survive about 70 to 80 cell divisions. This makes them less suitable for establishing cell lines for research. However, one advantage of EG cells is that they do not appear to generate tumours when transferred into the body, as embryonic stem cells do. This may make them potentially useful sources of transplant tissue and cell-based therapies.
  8. A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta. The endoderm is composed of the entire gut tube and the lungs, the ectoderm gives rise to the nervous system and skin, and the mesoderm gives rise to muscle, bone, blood—in essence, everything else that connects the endoderm to the ectoderm
  9. Every cell contains a complete copy of “the blueprint of life” DNA consists of two strands of nucleotides - 4 bases (A,G,T,C) 23 pairs of chromosomes If unwound and tied together, human DNA in one cell would stretch ~ 5 feet, but would be only 50 trillionths of an inch wide! Genes are specific sequences of DNA, each of which “codes” for a protein with a specific function Genes are copied each time a cell divides, passing on the blueprint
  10. The early stages of embryogenesis are the point at which embryonic stem cell lines are derived. The fertilized egg (day 1) undergoes cell division to form a 2-cell embryo, followed by 4-cell, etc. until a ball of cells is formed by the fourth day. The ball becomes hollow, forming the blastocyst. This is the stage at which pluripotent embryonic stem cell lines are generated. Following the blastocyst stage, the tissues of the embryo start to form and the cells become multipotent.
  11. The inner cell mass (the part that would form the fetus) of the embryo is isolated and disrupted to form embryonic cell lines. This process destroys the embryo. Under special culture conditions, the cells of the embryonic lines can be coaxed to form certain kinds of differentiated cell types. In theory, these differentiated cells could be used to repair or replace defective cells or tissues.
  12. New evidence suggests that bone marrow stem cells may be able to differentiate into cell types that make up tissues outside of the blood, such as liver and muscle. Scientists are exploring new uses for these stem cells that go beyond diseases of the blood. While most blood stem cells reside in the bone marrow, a small number are present in the bloodstream. These peripheral blood stem cells, or PBSCs, can be used just like bone marrow stem cells to treat leukemia, other cancers and various blood disorders. Since they can be obtained from drawn blood, PBSCs are easier to collect than bone marrow stem cells, which must be extracted from within bones. This makes PBSCs a less invasive treatment option than bone marrow stem cells. PBSCs are sparse in the bloodstream, however, so collecting enough to perform a transplant can pose a challenge.
  13. Human embryonic stem cells have been studied only recently, so their capabilities are, as of yet, unknown. In theory, the embryonic stem cells are able to form every cell type (which is what they do in the embryo). However, the conditions in culture might not be able to recreate the conditions that give rise to many tissues in the intact embryo. In addition to these unknowns, it is uncertain that the cultured stem cells will function the same as cells that have been developed within the embryo. For example, in a recent study, insulin-producing cells derived from murine embryonic stem cells failed to produce the insulin when transplanted into mice, but only formed tumors.1 In addition, it is uncertain that these lines will continue to proliferate indefinitely without undergoing genetic mutations that render them useless. According to the President's Council on Bioethics: "It is not yet known whether any preparation of human ES cells (generally believed to be much longer-lived than adult stem cells) will continue to grow 'indefinitely,' without undergoing genetic changes."2 References S. Sipione et al. 2004. Insulin expressing cells from differentiated embryonic stem cells are not beta cells. Diabetologia 47: 499-508. "Recent Developments in Stem Cell Research." Monitoring Stem Cell Research. The President's Council on Bioethics, January 2004.
  14. In order to be used clinically, human embryonic stem cells must be differentiated prior to use in patients. Undifferentiated stem cells could produce tumors and multiply unchecked within a patient, causing more problems than providing appropriate therapy. It is uncertain if conditions can be defined such that all embryonic stem cells differentiate into the correct cell type prior to therapeutic use. Complications caused by undifferentiated cells might not be discovered until years after the first clinical trials are begun. This differentiation problem is acknowledged on the International Society for Stem Cell Research website: "Scientists are still working on developing proper conditions to differentiate embryonic stem cells into specialized cells. As embryonic stem cells grow very fast, scientists must be very careful in fully differentiating them into specialized cells. Otherwise, any remaining embryonic stem cells can grow uncontrolled and form tumors."1 Recently, three established stem cell lines were shown to exhibit abnormalities in chromosome number and structure.2, 3 Obviously, stem cell lines must be checked periodically to make sure the cells do not become abnormal during continued culture. The use of abnormal cells in treatment of patients could result in indeterminate complications. References "Frequently Asked Questions." International Society for Stem Cell Research. Draper, J.S., et al., "Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells," Nature Biotechnology December 7, 2003, advance online publication. C. Cowan et al. 2004. Derivation of Embryonic Stem-Cell Lines from Human Blastocysts. New England Journal of Medicine 350: 1353-1356.
  15. Undifferentiated stem cells could produce tumors and multiply unchecked within a patient, causing more problems than providing appropriate therapy. According to a recent article ion the New England Journal of Medicine: "There are still many hurdles to clear before embryonic stem cells can be used therapeutically. For example, because undifferentiated embryonic stem cells can form tumors after transplantation in histocompatible animals, it is important to determine an appropriate state of differentiation before transplantation. Differentiation protocols for many cell types have yet to be established. Targeting the differentiated cells to the appropriate organ and the appropriate part of the organ is also a challenge.” Harvard scientists reported in the Proceedings of the National Academy of Sciences that five out of the 19 mice injected with embryonic stem cells developed tumors and died."2 Stem cell lines will suffer the same tissue rejection problems as adult transplants. Once differentiated, these cells will express the HLA tissue antigens programmed by their parental DNA. These antigens must match those of the recipient or else tissue rejection will occur. An admission of the problem of immune rejection can be found from The Scientist: "[W]ithin the [embryonic stem cell] research community, realism has overtaken early euphoria as scientists realize the difficulty of harnessing ESCs safely and effectively for clinical applications. After earlier papers in 2000 and 2001 identified some possibilities, research continued to highlight the tasks that lie ahead in steering cell differentiation and avoiding side effects, such as immune rejection and tumorigenesis.”1 References E. Phimister and J. Drazen. 2004. Two Fillips for Human Embryonic Stem Cells.” New England Journal of Medicine 350: 1351-1352. Bjorklund, L. M., R. Sanchez-Pernaute, et al. 2002 "Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model." Proceedings of the National Academy of Sciences 99: 2344-2349. Hunter, Philip. 2003. Differentiating Hope from Embryonic Stem Cells. The Scientist 17: 31.
  16. Like all immortal cell lines, embryonic stem cell lines must be protected and checked for contamination with viruses, bacteria, fungi, and Mycoplasma. The use of infected lines in patient treatment could have devastating effects. Many embryonic stem cell lines are grown using mouse feeder cells. The mouse cells help the embryonic lines to grow, but pose risks for transplantation due to compatibility problems in human bodies.1 Reference Kennedy, Donald. 2003. Stem Cells: Still Here, Still Waiting. Science 300: 865.
  17. Every cell contains a complete copy of “the blueprint of life” DNA consists of two strands of nucleotides - 4 bases (A,G,T,C) 23 pairs of chromosomes If unwound and tied together, human DNA in one cell would stretch ~ 5 feet, but would be only 50 trillionths of an inch wide! Genes are specific sequences of DNA, each of which “codes” for a protein with a specific function Genes are copied each time a cell divides, passing on the blueprint