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STEMCELL
THERAPY
STEM CELL THERAPY
Dr. Ashutosh Tiwari
M.D. Pharmacology 1st year
SAIMS Indore
21/03/2014
Outline
• History of Stem cell research
• What are stem cells
• Types & sources of stem cells
• Cultivation process
• Stem cells & cloning
• Potential uses
• Stem cell therapy
• Ethical issues
• Indian status
• Conclusions
Introduction
• Today living in the 21st century, we still do
not have proper treatments for many
diseases like diabetes, Parkinson's Disease,
Alzheimer's Disease etc.
• Some light of hope for the treatment of these
incurable diseases is - the Stem Cells
Introduction
• Research on stem cells is advancing
• How an organism develops from a single cell and how
healthy cells replace damaged cells in adult organisms.
• This promising area of science - investigates the possibility
of cell-based therapies to treat disease, which is often
referred to as regenerative or reparative medicine
History of Human Stem Cell Research
• In 1968, the first bone marrow transplant was
successfully used in treatment of Severe
Combined Immunodeficiency
• Since the 1970s, bone marrow transplants
have been used for treatment of
immunodeficiencies and leukemias
• In 1998, James Thomson (University of Wisconsin-Madison)
isolated cells from the inner cell mass of the early embryo,
and developed the first human embryonic stem cell lines.
History of Human Embryonic
Stem Cell Research
 In 1998, John Gearhart (Johns Hopkins
University) derived human embryonic germ
cells from cells in fetal gonadal tissue
(primordial germ cells).
 Pluripotent stem cell “lines” were developed
from both sources
History of Stem Cell
• 1999 - First Successful human transplant of insulin-
making cells from cadavers
• 2001 – First cloned human embryos (only to six cell
stage) created by Advanced Cell Technology (USA)
• 2004 - Harvard researchers grow stem cells from
embryos
 1998 – Mice cloned
 1998 – Cows cloned
• 1952 – Briggs and King cloned
tadpoles
• 1996 – The first mammal cloned from
adult cells was Dolly, the sheep.
 2000 – Pigs cloned
History of Somatic Cell Nuclear
Transfer (Cloning)
History of Cloning
 2001 – Cat cloned
 2002 – Rabbits cloned
 2003 – Mule cloned
 2004 – Bull cloned
 2005 – Dog cloned
Stem Cell – Definition
 A cell that has
the ability to
continuously
divide and
differentiate
(develop) into
various other
kind(s) of
cells/tissues
Properties of Stem Cell
All stem cells—regardless of their source have
three general properties
They are capable of dividing and renewing
themselves for long periods
They are unspecialized
They can give rise to specialized cell types
Stem cell
Stem cell
( unlimited
cell division )
Specialized cell
(e.g., white blood cell)
Self - Renewal (Regeneration)
• Stem cells are capable of dividing & renewing
themselves for long periods
– This is unlike muscle, blood or nerve cells – which
do not normally replicate themselves
– These cells are capable of long-term self-renewal
Unspecialization
• Stem Cells are unspecialized
– They do not have any tissue-specific structures
that allow for specialized function
Specialization of Stem Cells: Differentiation
• Differentiation: unspecialized stem cells give rise
to specialized (differentiated) cells in response to
external and internal chemical signals
– Internal signals: specific genes causing differential
gene expression
– External signals :
• Chemicals secreted by other cells such as growth factors,
cytokines, etc.
• Physical contact with neighboring cells
Stem cell Types
• Totipotent
– the ability to differintiate into all types; can form
any cell of the embryo as well as the placenta
– Ex: morula
• Pluripotent
– the ability to differentiate into almost all types
except placental tissue
– Ex: cells from inner cell mass of blastocyst
Stem cell Types
• Multipotent
– can differentiate into multiple specialized cells of a closely
related family of cells
– Ex: hematopoietic stem cells
• Oligopotent
– the ability to differentiate into a few cells
– Ex: lymphoid
• Unipotent
– these cells only produce one cell type., but have the property of
self renewal which distinguishes them from the non stem cells
– Ex: muscle stem cells, cardiac stem cells
Stem Cells
Adult stem cells
•
Function
To replace physiologically lost
cells
e.g. Blood (Hematopoietic
stem cells).
GIT epithelial cells
Skin & Hair (epidermis, hair
follicles, and sebaceous glands
are replaced by stem cells).
To divide in
response to tissue
injury or infection
e.g. Skeletal Muscle
regeneration as a
response to
exercise or injury
Human Stem Cells
Embryonic
Stem Cells
Fetal
Stem Cells
Infant Adult
Umbilical Cord Blood Stem Cells
Classification of Human Stem Cells
Umbilical cord Stem Cells
• At the time of delivery,
cord blood is collected,
stored, and frozen.
• UCB contains two
classes of stem cells.
– Haematopoietic stem
cells (HSC).
– Mesenchymal stem
cells (MSC).
• Can be used to cure
chronic blood-related
disorders such as sickle
cell disease, Thalasemia,
and leukaemia.
Amniotic Stem Cells
• Multipotent stem cells are found in amniotic fluid
• Amniotic stem cells can differentiate in cells of
adipogenic, osteogenic, myogenic, endothelial,
hepatic and also neuronal lines.
Fetal Stem cells
• derived from aborted fetal tissue
• Their ability to renew themselves is limited
• it is more difficult to produce normal tissues from these cells.
Embryonic Stem Cells
• Embryonic stem cells (ES cells) are derived from
the cells in the inner cell mass of the developing
blastocyst
• Human ES cells are derived from embryos that
developed from unused eggs that were fertilized
in vitro in an in vitro fertilization clinic
• They have been donated for research with
informed consent of the donors.
• Human ES cells are not derived from eggs
fertilized in a woman's body.
Derivation and Use of Embryonic
Stem Cell Lines
Isolate inner cell mass
(destroys embryo)
Heart muscleKidney
Liver
“Special sauce”
(largely unknown)
Day 5-6
Blastocyst
Inner cells
(forms fetus)
Outer cells
(forms placenta)
Heart
repaired
Culture cells
Adult Stem cells
• Bone Marrow Stem Cells
• Peripheral Blood Stem Cells
• Neuronal Stem Cells (from olfactory bulb, spinal cord)
• Muscle Stem Cells
• Liver Stem Cells
• Pancreatic Stem Cells
• Renal stem cells
• Corneal Limbal Stem Cells
• Dental pulp
Embryonic vs Adult Stem Cells
• Totipotent
– Differentiation into ANY cell
type
• Large numbers can be
harvested from embryos
• May cause immune
rejection
• Potential for undesired
tumor formation (teratoma)
• High ethical controversy &
uncertain legal status
• Multi or pluripotent
– Differentiation into some cell
types, limited outcomes
• Limited numbers, more
difficult to isolate
• Less likely to cause immune
rejection, since the patient’s
own cells can be used
• Less likely to form tumors
• Less moral & legal contoversy
Autologous Stem Cells
 Sources of the patient's own stem cells
(autologous) are either the cells from patient's
own body or his or her cord blood.
 For autologous transplants physicians now
usually collect stem cells from the peripheral
blood rather than the marrow
Allogenic Stem Cells
• Sources of stem cells from
another donor (allogeneic)
• are primarily relatives
(familial-allogeneic) or
completely unrelated
donors (unrelated-
allogeneic)
• The stem cells in this
situation are extracted from
either the donor's body or
cord blood
Cultivation of Stem Cell
• Embryonic stem (ES) cells
• Tissue (Adult) stem cells
• Induced pluripotent stem cells (iPS cells)
• Somatic cell nuclear transfer (therapeutic
cloning)
Embryonic stem (ES) cells:
blastocyst
outer layer of cells
= ‘trophectoderm’
cells inside
= ‘inner cell mass’
embryonic stem cells taken from
the inner cell mass
culture in the lab
to grow more cells
fluid with nutrients
Embryonic stem (ES) cells:
embryonic stem cells
PLURIPOTENT
all possible types of specialized
cells
differentiation
Tissue stem cells:
muscles
skin
surface of the eye brain
breast
intestines (gut)
bone marrow
testicles
Tissue stem cells:
MULTIPOTENT
blood stem cell
found in
bone marrow
differentiation
only specialized types of blood cell:
red blood cells, white blood cells,
platelets
Novel methods
• Extraction of single blastomere without damaging
embryo and developed into independent hESC lines
Chung et al ,Nature 2006; 439:216-19
• Altered Nuclear Technique (ANT)
genetically modifying the somatic nucleus so that
induced pluripotent stem cells are produced
Meissener & Jaenisch Nature 2006;439:212-15
• Somatic Cell Nuclear Transfer / Therapeutic cloning
Induced pluripotent stem cells
• derived from adult cells in
2007
• can be grown indefinitely in
culture in an undifferentiated
state
• similar properties to
embryonic stem cells as can
differentiate into many
different tissue types –
pluripotent
• can create stem cells directly
from a patient for research
• Advantage: no need for
embryos!
Induced change in
gene expression
pluripotent
stem cells
Starting cells from
donor tissue
iPS Cells
Induced pluripotent stem cell
cell from the body
‘genetic reprogramming’
= add certain genes to the cell
induced pluripotent stem (iPS)
cell
behaves like an embryonic stem
cell
all possible types of
specialized cells
culture iPS cells in the lab
differentiation
Somatic cell nuclear transfer
• A nucleus from an adult donor cell is inserted into
a recipient egg cell from which the nucleus has been
removed
•The resulting cell is then stimulated to divide as a
zygote later forming embryo genetically identical to
the adult donor cell
•May be ethically acceptable as embryos by
conventional methods are not used
Somatic cell nuclear transfer is an alternate
source of embryonic stem cells
Patient-Specific Stem Cells
Unfertilized egg Fusion with
patient’s cell
Fertilized egg
“equivalent”
Blastocyst
Stem cell work may bypass
objections / Ethical Issues
Stem-cell work may bypass
objections / Ethical Issues
Novel Methods
• Many questions remain to be explored before
these novel methods can be used in the clinic:
– are they really equivalent to human embryonic
stem cells?
– are they stable over a long time?
– will they be safe and effective for treatment?
Development in Stem
Cell Research
The patient’s lower limbs were
paralyzed after an accident in 1985;
damaged her lower back and hips.
Afterward she spent her life in bed or
in a wheelchair
The stem cell transplantation (adult
stem cells from umbilical cord
blood)was performed on Oct. 12,
2004 and in just three weeks she
started to walk with the help of a
walker.
Regenerative Medicine
For the first time researchers
reconstitute a complete organ.
New bladders were made by
growing bladder cells from the
patients on a biodegradable
scaffolding.
- Reported in the
Lancet (April, 2006)
World's first transplant of a whole
organ grown in lab
• November 2008
• Claudia Castillo
• damaged windpipe
• lower chance of rejection
Potential Uses of Stem Cells
• Basic research – clarification of complex
events that occur during human development
& understanding molecular basis of cancer
– Molecular mechanisms for gene control
– Role of signals in gene expression & differentiation
of the stem cell
– Stem cell theory of cancer
Potential uses cont.
• Biotechnology(drug discovery & development)
– stem cells can provide specific cell types to
test new drugs
– Safety testing of new drugs on differentiated cell
lines
– Screening of potential drugs
• Cancer cell lines are already being used to screen
potential anti-tumor drugs
• Availability of pluripotent stem cells would allow drug
testing in a wider range of cell types & to reduce animal
testing
Potential uses cont.
• Cell based therapies:
– Regenerative therapy to treat Parkinson’s,
Alzheimer’s, spinal cord injury, stroke, severe
burns, heart disease, diabetes, osteoarthritis, and
rheumatoid arthritis
– Stem cells in gene therapy
• Stem cells as vehicles after they have been genetically
manipulated
– Stem cells in therapeutic cloning
– Stem cells in cancer
STEM CELL THERAPY
• Stem cell therapy is introduction of new adult
stem cells into damaged tissue in order to treat
disease or injury.
• The ability of stem cells to self-renew and give
rise to different cells, that can potentially replace
diseased and damaged areas in the body, with
minimal risk of rejection and side effects.
• A number of stem cell therapies exist, but most
are at experimental stages, costly or
controversial.
What Diseases Can be
Cured by Stem Cell Therapies?
►Any disease in which there is tissue degeneration can
be a potential candidate for stem cell therapies
Alzheimer’s disease
Parkinson’s disease
Spinal cord injury
Heart disease
Severe burns
Diabetes
Tissue Repair
• Regenerate spinal cord, heart
tissue or any other major tissue in
the body.
Heart Disease
• Adult bone marrow stem cells injected
into the hearts are believed to improve
cardiac function in victims of heart failure
or heart attack
Leukemia and Cancer
• Leukemia patients treated with stem
cells emerge free of disease.
• Stem cells have also reduces
pancreatic cancers in some patients.
Proliferation of white cells
Rheumatoid Arthritis
• Adult Stem Cells may be helpful in
starting repair of eroded cartilage.
Type I Diabetes
• Embryonic Stems Cells might be trained
to become pancreatic islets cells needed
to secrete insulin.
Challenges to Stem Cell Research
• Source - Cell lines may have mutations
• Delivery to target areas
• Prevention of rejection
• Suppressing tumors
• Stem Cell regenerated tissue viability
• Political and religious obstructions
• Inability to obtain source material due to ethical
concerns
EMBRYONIC STEM CELL CONTROVERSY
• There is wide-spread controversy over the use of
human embryonic stem cells. This controversy primarily
targets the techniques used to derive new embryonic stem
cell lines, which often requires the destruction of
the blastocyst.
• At present, there are alternative sources for stem cells which
have achieved considerable success when used as medical
therapies. These alternatives do not require the destruction of
an embryo, such as the use of umbilical cord blood, milky
teeth stem cells, bone marrow stem cells or using induced
pluripotent stem cells.
• However, non-embryonic stem cells may have limitations.
The Ethical Debate
In favor of ESCR:
• Embryonic stem cell research
(ESCR) fulfills the ethical obligation
to alleviate human suffering.
• Since excess IVF embryos will be
discarded anyway, isn’t it better
that they be used in valuable
research?
• SCNT (Therapeutic Cloning)
produces cells in a petri dish, not a
pregnancy.
Against ESCR:
• In ESCR, stem cells are taken
from a human blastocyst, which
is then destroyed. This amounts
to “murder.”
• There is a risk of commercial
exploitation of the human
participants in ESCR.
• ESCR will lead to reproductive
cloning.
Day 5-6
Blastocyst
Stem Cell Ethics
• This is an ethical issue.
• Science is designed to tell us what is possible –
what we can do.
• Science is not designed to tell us what is right
– what we should do.
• To evaluate this technology one must employ
some ethical system that comes from outside
of science.
Stem Cell Ethics
• “Can we” vs. “Should we”
– Dramatic advances of modern molecular genetics
– Should we ask the morality questions before
attempting the “can we” questions?
Stem Cell Ethics
• Encourage development of sound research and
therapy.
• Prevent any misuse of human embryos and
fetuses.
• Protect patients from fraudulent treatments in
the name of stem cell research
Current status in India
• Keeping in view of its potential therapeutic
applications, both basic and translational research are
being promoted in various institutions, hospitals and
the industry.
• Till date, more than 55 programmes have been
identified and supported on various aspects of stem
cell research.
ALL INDIA INSTITUTE OF
MEDICAL SCIENCES
NEW DELHI
National Institute for Research
in Reproductive Health (ICMR)
Mumbai
National Center for Cell
Science, Pune
Rajiv Gandhi Center for
Biotechnology
Trivandrum , Kerala, India
Center for Cellular and Molecular
Biology, Hyderabad
The Stem Cell Institute (SCSRM)
Center for Cellular and Molecular
Platforms
Karnataka
Stem Cell research: Indian Guidelines
• Due to ethical and religious concerns related to
research with human embryos, the Indian
Government has decided to come clear on the
scope and purview of stem cell research in the
country.
• National Guidelines for Stem Cell Research
was published by ICMR in 2013.
Stem Cell research: Indian Guidelines
Conclusions
►Stem cells show great promise for regenerative medicine
►There is enormous potential in human stem cell research
Both adult and embryonic stem cells should be studied
►Much research needed before therapies are realized
►Ethical concerns need to be taken into account
►Proper guidelines are needed to ensure appropriate conduct
of the research
THANK YOU!
STEM CELLS CAN
CREATE MIRACLES…
GIVE HOPE TO THE
HOPELESS…
REWRITE MEDICAL
SCIENCE
&
COULD MAKE LIFE
IMMORTAL!!!

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Stem cell therapy

  • 2. STEM CELL THERAPY Dr. Ashutosh Tiwari M.D. Pharmacology 1st year SAIMS Indore 21/03/2014
  • 3. Outline • History of Stem cell research • What are stem cells • Types & sources of stem cells • Cultivation process • Stem cells & cloning • Potential uses • Stem cell therapy • Ethical issues • Indian status • Conclusions
  • 4. Introduction • Today living in the 21st century, we still do not have proper treatments for many diseases like diabetes, Parkinson's Disease, Alzheimer's Disease etc. • Some light of hope for the treatment of these incurable diseases is - the Stem Cells
  • 5. Introduction • Research on stem cells is advancing • How an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. • This promising area of science - investigates the possibility of cell-based therapies to treat disease, which is often referred to as regenerative or reparative medicine
  • 6. History of Human Stem Cell Research • In 1968, the first bone marrow transplant was successfully used in treatment of Severe Combined Immunodeficiency • Since the 1970s, bone marrow transplants have been used for treatment of immunodeficiencies and leukemias
  • 7. • In 1998, James Thomson (University of Wisconsin-Madison) isolated cells from the inner cell mass of the early embryo, and developed the first human embryonic stem cell lines. History of Human Embryonic Stem Cell Research  In 1998, John Gearhart (Johns Hopkins University) derived human embryonic germ cells from cells in fetal gonadal tissue (primordial germ cells).  Pluripotent stem cell “lines” were developed from both sources
  • 8. History of Stem Cell • 1999 - First Successful human transplant of insulin- making cells from cadavers • 2001 – First cloned human embryos (only to six cell stage) created by Advanced Cell Technology (USA) • 2004 - Harvard researchers grow stem cells from embryos
  • 9.  1998 – Mice cloned  1998 – Cows cloned • 1952 – Briggs and King cloned tadpoles • 1996 – The first mammal cloned from adult cells was Dolly, the sheep.  2000 – Pigs cloned History of Somatic Cell Nuclear Transfer (Cloning)
  • 10. History of Cloning  2001 – Cat cloned  2002 – Rabbits cloned  2003 – Mule cloned  2004 – Bull cloned  2005 – Dog cloned
  • 11. Stem Cell – Definition  A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues
  • 12. Properties of Stem Cell All stem cells—regardless of their source have three general properties They are capable of dividing and renewing themselves for long periods They are unspecialized They can give rise to specialized cell types
  • 13. Stem cell Stem cell ( unlimited cell division ) Specialized cell (e.g., white blood cell)
  • 14. Self - Renewal (Regeneration) • Stem cells are capable of dividing & renewing themselves for long periods – This is unlike muscle, blood or nerve cells – which do not normally replicate themselves – These cells are capable of long-term self-renewal
  • 15. Unspecialization • Stem Cells are unspecialized – They do not have any tissue-specific structures that allow for specialized function
  • 16. Specialization of Stem Cells: Differentiation • Differentiation: unspecialized stem cells give rise to specialized (differentiated) cells in response to external and internal chemical signals – Internal signals: specific genes causing differential gene expression – External signals : • Chemicals secreted by other cells such as growth factors, cytokines, etc. • Physical contact with neighboring cells
  • 17. Stem cell Types • Totipotent – the ability to differintiate into all types; can form any cell of the embryo as well as the placenta – Ex: morula • Pluripotent – the ability to differentiate into almost all types except placental tissue – Ex: cells from inner cell mass of blastocyst
  • 18. Stem cell Types • Multipotent – can differentiate into multiple specialized cells of a closely related family of cells – Ex: hematopoietic stem cells • Oligopotent – the ability to differentiate into a few cells – Ex: lymphoid • Unipotent – these cells only produce one cell type., but have the property of self renewal which distinguishes them from the non stem cells – Ex: muscle stem cells, cardiac stem cells
  • 20. Adult stem cells • Function To replace physiologically lost cells e.g. Blood (Hematopoietic stem cells). GIT epithelial cells Skin & Hair (epidermis, hair follicles, and sebaceous glands are replaced by stem cells). To divide in response to tissue injury or infection e.g. Skeletal Muscle regeneration as a response to exercise or injury
  • 21. Human Stem Cells Embryonic Stem Cells Fetal Stem Cells Infant Adult Umbilical Cord Blood Stem Cells Classification of Human Stem Cells
  • 22. Umbilical cord Stem Cells • At the time of delivery, cord blood is collected, stored, and frozen. • UCB contains two classes of stem cells. – Haematopoietic stem cells (HSC). – Mesenchymal stem cells (MSC). • Can be used to cure chronic blood-related disorders such as sickle cell disease, Thalasemia, and leukaemia.
  • 23. Amniotic Stem Cells • Multipotent stem cells are found in amniotic fluid • Amniotic stem cells can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.
  • 24. Fetal Stem cells • derived from aborted fetal tissue • Their ability to renew themselves is limited • it is more difficult to produce normal tissues from these cells.
  • 25. Embryonic Stem Cells • Embryonic stem cells (ES cells) are derived from the cells in the inner cell mass of the developing blastocyst • Human ES cells are derived from embryos that developed from unused eggs that were fertilized in vitro in an in vitro fertilization clinic • They have been donated for research with informed consent of the donors. • Human ES cells are not derived from eggs fertilized in a woman's body.
  • 26. Derivation and Use of Embryonic Stem Cell Lines Isolate inner cell mass (destroys embryo) Heart muscleKidney Liver “Special sauce” (largely unknown) Day 5-6 Blastocyst Inner cells (forms fetus) Outer cells (forms placenta) Heart repaired Culture cells
  • 27. Adult Stem cells • Bone Marrow Stem Cells • Peripheral Blood Stem Cells • Neuronal Stem Cells (from olfactory bulb, spinal cord) • Muscle Stem Cells • Liver Stem Cells • Pancreatic Stem Cells • Renal stem cells • Corneal Limbal Stem Cells • Dental pulp
  • 28. Embryonic vs Adult Stem Cells • Totipotent – Differentiation into ANY cell type • Large numbers can be harvested from embryos • May cause immune rejection • Potential for undesired tumor formation (teratoma) • High ethical controversy & uncertain legal status • Multi or pluripotent – Differentiation into some cell types, limited outcomes • Limited numbers, more difficult to isolate • Less likely to cause immune rejection, since the patient’s own cells can be used • Less likely to form tumors • Less moral & legal contoversy
  • 29. Autologous Stem Cells  Sources of the patient's own stem cells (autologous) are either the cells from patient's own body or his or her cord blood.  For autologous transplants physicians now usually collect stem cells from the peripheral blood rather than the marrow
  • 30. Allogenic Stem Cells • Sources of stem cells from another donor (allogeneic) • are primarily relatives (familial-allogeneic) or completely unrelated donors (unrelated- allogeneic) • The stem cells in this situation are extracted from either the donor's body or cord blood
  • 31. Cultivation of Stem Cell • Embryonic stem (ES) cells • Tissue (Adult) stem cells • Induced pluripotent stem cells (iPS cells) • Somatic cell nuclear transfer (therapeutic cloning)
  • 32. Embryonic stem (ES) cells: blastocyst outer layer of cells = ‘trophectoderm’ cells inside = ‘inner cell mass’ embryonic stem cells taken from the inner cell mass culture in the lab to grow more cells fluid with nutrients
  • 33. Embryonic stem (ES) cells: embryonic stem cells PLURIPOTENT all possible types of specialized cells differentiation
  • 34. Tissue stem cells: muscles skin surface of the eye brain breast intestines (gut) bone marrow testicles
  • 35. Tissue stem cells: MULTIPOTENT blood stem cell found in bone marrow differentiation only specialized types of blood cell: red blood cells, white blood cells, platelets
  • 36. Novel methods • Extraction of single blastomere without damaging embryo and developed into independent hESC lines Chung et al ,Nature 2006; 439:216-19 • Altered Nuclear Technique (ANT) genetically modifying the somatic nucleus so that induced pluripotent stem cells are produced Meissener & Jaenisch Nature 2006;439:212-15 • Somatic Cell Nuclear Transfer / Therapeutic cloning
  • 37. Induced pluripotent stem cells • derived from adult cells in 2007 • can be grown indefinitely in culture in an undifferentiated state • similar properties to embryonic stem cells as can differentiate into many different tissue types – pluripotent • can create stem cells directly from a patient for research • Advantage: no need for embryos! Induced change in gene expression pluripotent stem cells Starting cells from donor tissue iPS Cells
  • 38. Induced pluripotent stem cell cell from the body ‘genetic reprogramming’ = add certain genes to the cell induced pluripotent stem (iPS) cell behaves like an embryonic stem cell all possible types of specialized cells culture iPS cells in the lab differentiation
  • 39. Somatic cell nuclear transfer • A nucleus from an adult donor cell is inserted into a recipient egg cell from which the nucleus has been removed •The resulting cell is then stimulated to divide as a zygote later forming embryo genetically identical to the adult donor cell •May be ethically acceptable as embryos by conventional methods are not used
  • 40. Somatic cell nuclear transfer is an alternate source of embryonic stem cells Patient-Specific Stem Cells Unfertilized egg Fusion with patient’s cell Fertilized egg “equivalent” Blastocyst
  • 41. Stem cell work may bypass objections / Ethical Issues
  • 42. Stem-cell work may bypass objections / Ethical Issues
  • 43. Novel Methods • Many questions remain to be explored before these novel methods can be used in the clinic: – are they really equivalent to human embryonic stem cells? – are they stable over a long time? – will they be safe and effective for treatment?
  • 44. Development in Stem Cell Research The patient’s lower limbs were paralyzed after an accident in 1985; damaged her lower back and hips. Afterward she spent her life in bed or in a wheelchair The stem cell transplantation (adult stem cells from umbilical cord blood)was performed on Oct. 12, 2004 and in just three weeks she started to walk with the help of a walker.
  • 45. Regenerative Medicine For the first time researchers reconstitute a complete organ. New bladders were made by growing bladder cells from the patients on a biodegradable scaffolding. - Reported in the Lancet (April, 2006)
  • 46. World's first transplant of a whole organ grown in lab • November 2008 • Claudia Castillo • damaged windpipe • lower chance of rejection
  • 47. Potential Uses of Stem Cells • Basic research – clarification of complex events that occur during human development & understanding molecular basis of cancer – Molecular mechanisms for gene control – Role of signals in gene expression & differentiation of the stem cell – Stem cell theory of cancer
  • 48. Potential uses cont. • Biotechnology(drug discovery & development) – stem cells can provide specific cell types to test new drugs – Safety testing of new drugs on differentiated cell lines – Screening of potential drugs • Cancer cell lines are already being used to screen potential anti-tumor drugs • Availability of pluripotent stem cells would allow drug testing in a wider range of cell types & to reduce animal testing
  • 49. Potential uses cont. • Cell based therapies: – Regenerative therapy to treat Parkinson’s, Alzheimer’s, spinal cord injury, stroke, severe burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis – Stem cells in gene therapy • Stem cells as vehicles after they have been genetically manipulated – Stem cells in therapeutic cloning – Stem cells in cancer
  • 50. STEM CELL THERAPY • Stem cell therapy is introduction of new adult stem cells into damaged tissue in order to treat disease or injury. • The ability of stem cells to self-renew and give rise to different cells, that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects. • A number of stem cell therapies exist, but most are at experimental stages, costly or controversial.
  • 51. What Diseases Can be Cured by Stem Cell Therapies? ►Any disease in which there is tissue degeneration can be a potential candidate for stem cell therapies Alzheimer’s disease Parkinson’s disease Spinal cord injury Heart disease Severe burns Diabetes
  • 52. Tissue Repair • Regenerate spinal cord, heart tissue or any other major tissue in the body.
  • 53. Heart Disease • Adult bone marrow stem cells injected into the hearts are believed to improve cardiac function in victims of heart failure or heart attack
  • 54. Leukemia and Cancer • Leukemia patients treated with stem cells emerge free of disease. • Stem cells have also reduces pancreatic cancers in some patients. Proliferation of white cells
  • 55. Rheumatoid Arthritis • Adult Stem Cells may be helpful in starting repair of eroded cartilage.
  • 56. Type I Diabetes • Embryonic Stems Cells might be trained to become pancreatic islets cells needed to secrete insulin.
  • 57. Challenges to Stem Cell Research • Source - Cell lines may have mutations • Delivery to target areas • Prevention of rejection • Suppressing tumors • Stem Cell regenerated tissue viability • Political and religious obstructions • Inability to obtain source material due to ethical concerns
  • 58. EMBRYONIC STEM CELL CONTROVERSY • There is wide-spread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. • At present, there are alternative sources for stem cells which have achieved considerable success when used as medical therapies. These alternatives do not require the destruction of an embryo, such as the use of umbilical cord blood, milky teeth stem cells, bone marrow stem cells or using induced pluripotent stem cells. • However, non-embryonic stem cells may have limitations.
  • 59. The Ethical Debate In favor of ESCR: • Embryonic stem cell research (ESCR) fulfills the ethical obligation to alleviate human suffering. • Since excess IVF embryos will be discarded anyway, isn’t it better that they be used in valuable research? • SCNT (Therapeutic Cloning) produces cells in a petri dish, not a pregnancy.
  • 60. Against ESCR: • In ESCR, stem cells are taken from a human blastocyst, which is then destroyed. This amounts to “murder.” • There is a risk of commercial exploitation of the human participants in ESCR. • ESCR will lead to reproductive cloning. Day 5-6 Blastocyst
  • 61. Stem Cell Ethics • This is an ethical issue. • Science is designed to tell us what is possible – what we can do. • Science is not designed to tell us what is right – what we should do. • To evaluate this technology one must employ some ethical system that comes from outside of science.
  • 62. Stem Cell Ethics • “Can we” vs. “Should we” – Dramatic advances of modern molecular genetics – Should we ask the morality questions before attempting the “can we” questions?
  • 63. Stem Cell Ethics • Encourage development of sound research and therapy. • Prevent any misuse of human embryos and fetuses. • Protect patients from fraudulent treatments in the name of stem cell research
  • 64. Current status in India • Keeping in view of its potential therapeutic applications, both basic and translational research are being promoted in various institutions, hospitals and the industry. • Till date, more than 55 programmes have been identified and supported on various aspects of stem cell research.
  • 65. ALL INDIA INSTITUTE OF MEDICAL SCIENCES NEW DELHI National Institute for Research in Reproductive Health (ICMR) Mumbai National Center for Cell Science, Pune Rajiv Gandhi Center for Biotechnology Trivandrum , Kerala, India Center for Cellular and Molecular Biology, Hyderabad The Stem Cell Institute (SCSRM) Center for Cellular and Molecular Platforms Karnataka
  • 66. Stem Cell research: Indian Guidelines • Due to ethical and religious concerns related to research with human embryos, the Indian Government has decided to come clear on the scope and purview of stem cell research in the country. • National Guidelines for Stem Cell Research was published by ICMR in 2013.
  • 67. Stem Cell research: Indian Guidelines
  • 68. Conclusions ►Stem cells show great promise for regenerative medicine ►There is enormous potential in human stem cell research Both adult and embryonic stem cells should be studied ►Much research needed before therapies are realized ►Ethical concerns need to be taken into account ►Proper guidelines are needed to ensure appropriate conduct of the research
  • 70. STEM CELLS CAN CREATE MIRACLES… GIVE HOPE TO THE HOPELESS… REWRITE MEDICAL SCIENCE & COULD MAKE LIFE IMMORTAL!!!