stem cell
TRANSCRIPT
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 200 different cells
Differentiate into cells of the 3 germ cell layers
Because of their capacity of unlimited expansion and pluripotency – useful in regenerative medicine
Adult stem cells
They produce cells specific to the tissue in which they are found.
They are relatively unspecialized
However they are predetermined to give rise to specific cell types when they differentiatee.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
Totipotent Each cell can develop into a new individual
Cells from early (1-3 days) embryos
Pluripotent Cells 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
- rare specialized 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)
Isolate inner cell mass(destroys embryo)
Heart muscleKidney
Liver
“Special sauce”
Day 5-6BlastocystDay 5-6
Blastocyst
Inner cells(forms fetus)Inner cells
(forms fetus)
Outer cells(forms placenta)
Outer cells(forms placenta)
Heartrepaired
Culture cellsCulture 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 TherapyReplaceable tissues/organsRepair of defective cell typesDelivery of genetic therapiesDelivery 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 diagnosisIntrauterine stem cell transplantationGene 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 engraftment2. More tolerant to tissue matches3. Less severe GVHD4. Rarely contaminated with latent
virus5. Easy to collect, not painful6. Superior proliferative capacity7. Greater immunological naievity8. Unlimited supply9. Lower cost
Ailments for which stem cells are being used now
Acute leukemiasChronic leukemias
Myelodysplastic syndromes
Marrow failureMyeloproliferative disorders
Lymphoproliferative disorders
Phagocyte disordersInherited disorders like Lesch Nyhan syndrome,
beta Thallesemia etcInherited platelet abnormalities Inherited metabolic disorders like
Mucopolysaccharidosis, Hurler’s syndrome, Krabbe disease, Niemann- pick disease etc.
Histocytic disordersInherited erythrocyte abnormalitiesInherited immune system disorders like ataxia
telangectesia, DiGeorge syndrome, SCID etcPlasma cell disorderMalignancies like neuroblastoma, Ewing sarcoma,
Renal cell CA etc
Future stem cell applicationAlzheimer’s DiseaseLupusRheumatoid 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 IssuesThe 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 IndiaCompulsory 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 allowedTermination 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 IndiaResearch into human cloning is not to be doneThese 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.
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