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.