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Stem Cell therapy:
Status and Ethics
ARIJIT BHATTACHARJEE
WORKSHOP ON
EMERGING AREAS OF MOLECULAR BIOLOGY AND IMMUNOLOGY, 21ST MAY- 26TH MAY , 2012,.KARIMGANJ COLLEGE , KARIMGANJ, ASSAM.
Stem cellA cell that has the ability to continuously divide and differentiate (develop)
into various other kind(s) of cells/tissues . In mammals there are two broad
kinds of stem cells: Embryonic stem cells and Adult stem cells. The stem
cells and progenitor cells acts as a repair system for the body replenishing
adult tissues.
Identical stem cells
Stem cell
SELF-RENEWAL(copying)
Stem cell
Specialized cells
DIFFERENTIATION(specializing)
Comparison of Embryonic and Adult stem cells
Embryonic stem cell
Derived from the inner cell mass
Pluripotent
Can develop into more than 200different cells
Differentiate into cells of the 3germ cell layers
Because of their capacity ofunlimited expansion andpluripotency – useful inregenerative medicine
Adult stem cells
They produce cells specific to thetissue in which they are found.
They are relatively unspecialized
However they are predetermined to
give rise to specific cell types whenthey differentiate
e.g: haematopoietic, bone marrow,neural
Stem Cell Properties:
Self renewal - the ability to go through numerous cycles of cell division while
maintaining the undifferentiated state.
Potency – the capacity to differentiate into specialized cell types.
Totipotent stem cells -cells produced by the first few divisions of the cell . So can
form any cell of the embryo as well as the placenta.
Pluripotent – these cells differentiate into cells derived from the three germ cell
layers. e. g. haematopoietic stem cells, neural and mesenchymal stem cells.
Multipotent – these cells can produce cells of a closely related family of cells. e.g.:
haematopoietic stem cells, neural and mesenchymal stem cells.
Unipotent – these cells only produce one cell type., but have the property of self
renewal which distinguishes them from the non stem cells.
1 stem cell
Self renewal - maintains the stem cell pool
4 specialized cells
Differentiation - replaces dead or damagedcells throughout your life
Why self-renew AND differentiate?1 stem cell
Stem cell type Description Examples
TotipotentEach cell can develop into a new individual
Cells from early (1-3 days) embryos
PluripotentCells can form any (over 200) cell types
Some cells of blastocyst (5 to 14 days)
MultipotentCells differentiated, but can form a number of other tissues
Fetal tissue, cord blood, and adult stem cells
Kinds of Stem Cells/ stem cell jargon
Stem Cell Differentiation
TYPES OF STEM CELLS:
EMBRYONIC STEM CELL:FOUND IN INNER LAYER OF
BLASTOCYST- Differentiates into specialized cells.
TISSUE STEM CELL: FOUND IN DIFFERENT TISSUES
LIKE BONE MARROW, MUSCLE, ETC. Differentiates into
various specialized cell types like blood cells.
INDUCED PLURIPOTENT(iPS) STEM CELLS: Adult
cells which genetically reprogrammed to add certain genes, they
behave like embryonic stem cell and differentiate into specialized
cells.
ADVANTAGES OF iPS CELLS: No Need for
Embryos!!!!!!!!!!!
WORKSHOP ON EMERGING AREAS ON
MOLECULAR BIOLOGY AND IMMUNOLOGY,MAY 21-
MAY 26, 2012, KARIMGANJ COLLEGE , KARIMGANJ
WORKSHOP ON EMERGING AREAS ON
MOLECULAR BIOLOGY AND IMMUNOLOGY,MAY 21-
MAY 26, 2012, KARIMGANJ COLLEGE , KARIMGANJ
Where are stem cells found?
embryonic stem cellsblastocyst - a very early embryo
tissue stem cellsfetus, baby and throughout life
Stem cell niches
Direct contact Soluble factors Intermediate cell
stem cell
niche
NicheMicroenvironment around stem cells that provides support and signals regulating self-renewal and differentiation
Tens of thousands of frozen
embryos are routinely
destroyed when couples finish
their treatment.
These surplus embryos can
be used to produce stem cells.
Regenerative medical
research aims to develop these
cells into new, healthy tissue
to heal severe illnesses.
Tissue stem cells:
Principles of renewing tissues
Stem cell
committed progenitors:- “transient amplifying cells”
- multipotent- divide rapidly
- no self-renewal
stem cell:- self renew
- divide rarely- high potency
- rarespecialized cells:
- work- no division
EXAMPLES OF SUCH STEM CELL INCLUDE HSCs, NSCs AND GSCs, etc.
Tissue stem cells:
Haematopoietic stem cells (HSCs)
HSC
committed progenitors
neutrophil
NK cell
erythrocytes
dendritic cell
plateletsmegakaryocyte
macrophage
eosinophil
basophil
B cell
T cell
specialized cells
bone marrow
Tissue stem cells:
Neural stem cells (NSCs)
NSC
braincommitted progenitors specialized cells
Neurons
Interneurons
Oligodendrocytes
Type 2 Astrocytes
Type 1 Astrocytes
Tissue stem cells:
Gut stem cells (GSCs)
GSC
Small intestinecommitted progenitors
Columnar cells
Goblet cells
Endocrine cells
specialized cells
Islet cells
Tissue stem cells:
Mesenchymal stem cells (MSCs)
MSC
bone marrow
committed progenitors
Bone (osteoblasts)
Cartilage (chondrocytes)
Fat (adipocytes)
specialized cells
APPLICATIONS OF STEM CELL IN
BIOMEDICAL RESEARCH AND
REGENERATIVE MEDICINE
Derivation and Use of Embryonic Stem Cell
Lines
Isolate inner cell mass(destroys embryo)
Heart muscleKidney
Liver
“Special sauce”
Day 5-6Blastocyst
Inner cells(forms fetus)
Outer cells(forms placenta)
Heartrepaired
Culture cells
Somatic Cell Nuclear Transfer
The nucleus of a donated
egg is removed and replaced
with the nucleus of a mature,
"somatic cell" (a skin cell, for
example).
No sperm is involved in this
process, and no embryo is
created to be implanted in a
woman’s womb.
The resulting stem cells can
potentially develop into
specialized cells that are useful
for treating severe illnesses.
WORKSHOP ON EMERGING AREAS ON
MOLECULAR BIOLOGY AND IMMUNOLOGY,MAY 21-
MAY 26, 2012, KARIMGANJ COLLEGE , KARIMGANJ
SCNT CONT…
Stem Cell Cultivation
Human Stem Cell
Production
Possible Uses of Stem Cell
Therapy Replaceable tissues/organs
Repair of defective cell types
Delivery of genetic therapies
Delivery chemotherapeutic agents
In theory, stem cell technology could be used to produce replaceable tissues or organs.
Defective tissues/organs could be repaired using healthy cells. It would also be possible to
genetically engineer stem cells to accomplish activities that they would not ordinarily be
programmed to do. Part of this engineering could involve the delivery of chemotherapeutic
agents for treatment of cancers and tumors.
Potential application of fetal stem cells In
the field of fetal medicine: Non invasive prenatal diagnosis
Intrauterine stem cell transplantation
Gene therapy
Therapeutic applications of embryonic stem
cells –ES cell
The potential to form 200 or more cells.
Hence used in regenerative medicine in cases like cardiac failure, Parkinson's disease, diabetes.
These cells are being coaxed to differentiate into cardiomyocytes, neural stem cells, insulin producing cell and even germ cells.
Fig.
Induced Pluripotent Stem (iPS) cell in Regenerative
medicine
Blood is collected from umbilical cord immediately after delivery about 100-150cc
The number of cells in 1 ml is 40,000
They are stored in blood banks at -196deg celsius in a state of suspended animation and restart their activity on thawing.
Advantages over bone marrow cells
1. High rate of engraftment
2. More tolerant to tissue matches
3. Less severe GVHD
4. Rarely contaminated with latent virus
5. Easy to collect, not painful
6. Superior proliferative capacity
7. Greater immunological naievity
8. Unlimited supply
9. Lower cost
Ailments for which stem cells are being used now
Acute leukemias
Chronic leukemias
Myelodysplastic syndromes
Marrow failure
Myeloproliferative disorders
Lymphoproliferative disorders
Phagocyte disorders
Inherited disorders like Lesch Nyhan syndrome, beta Thallesemia etc
Inherited platelet abnormalities
Inherited metabolic disorders like Mucopolysaccharidosis, Hurler’s syndrome, Krabbe disease, Niemann- pick disease etc.
Histocytic disorders
Inherited erythrocyte abnormalities
Inherited immune system disorders like ataxia
telangectesia, DiGeorge syndrome, SCID etc
Plasma cell disorder
Malignancies like neuroblastoma, Ewing sarcoma, Renal
cell CA etc
Future stem cell application
Alzheimer’s Disease
Lupus
Rheumatoid arthritis
The Ethical DebateIn 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.
Slippery slope argument: ESCR will lead to reproductive cloning.
Key Ethical Issues The blastocyst used in stem cell research is
microscopically small and has no nervous system. Does it count as a “person” who has a right to life?
What do various religions say about when personhood begins? Does science have a view on this?
In a society where citizens hold diverse religious views, how can we democratically make humane public policy?
Guidelines for stem cell research in India Compulsory registration of the existing cell lines to be registered under
specific apex bodies in the field
Genetic research dealing with human egg or sperm and genetic engineering and then transfer of human blastocysts will not be allowed
Research and therapy using fetal/placental stem cell will be allowed
Termination of pregnancy cannot be sought for donating fetal tissue for therapeutic or financial benefits
All the umbilical cord blood banks should be registered with Drug Controller General of India
Research into human cloning is not to be done
These guidelines are aimed to encourage development of sound research and therapy, prevent any misuse of human embryos and fetuses and protect patients from fraudulent treatments in the name of stem cell research.