NAME: SALMA GULL

Roll number: 18BsZOL28760

Programme: Bs Zoology
Seminar topic:-

STEM CELL TECHNOLOGY

Outline:

 Stem cell characteristics

 Features of stem cells

 Embryonic stem cells(ESC)

 Adult stem cells(ASC)

 Classification of stem cells

 Culture and stem cell therapy

 Recent development
What is stem cell?

 A stem cell are unspecialized cells which differentiate and form specialized cells of
different types
 A stem cell is essentially the building block of human body
 Stem cells are the proginator cells that are capable of self-renewal and differentiation
into many different cell lineages
 Stem cell have potential for treatment of many malignant and non-malignant diseases

 Features of stem cells:

1. Stem cells are very unique cells.
2. Stem cells have amazing ability to develop into several distinct cell types in the
body
3. Stem cell can be used as repair system for the body
4. Stem cell can theoretically divide without limit in a living organism in order to
replenish various type of cells
 5. When a stem cell divides,each new cell has the potential to either remain a stem cell
or become another type of cell with a more specialized function(i.ea muscle cell ,a
red blood cell, a brain cell etc)

Three unique properties of stem cells:

I. Stem cells are capable of dividing and renewing themselves for the
long periods.
II. They are unspecialized and give rise to specialized cell types.
III. A stem cell is “uncommited”, untill it receives a signal to develop into
specialized cell.
 Asymmetric division of stem cells:
 Stem cell has ability to divide asymmetrically.
 One portion of the cell division becomes a differentiated cell while the
other becomes another stem cel
 Stem cells are capable of dividing and renewing themselves for long periods:
 Stem cells may replicate many times.
 When cells replicate themselves many times it is called prolifiration.
 The stem cells that proliferate for many months in the laboratory can yield
millions of cells.
 Stem cells are capable of long term self- renewal.
 Stem cells exist in both embryos and adults:
 In embryos, stem cells function to generate new organs and tissues.
 In adults,they function to replace cells during the natural course of cell turn
over.

Stem cells forming all cells of body:-

All cells of our body come from stem cells like muscle cells, stem cells, nerve cells, skin cells,
blood cells and the mechanism by which this happens can be understood by comparing with a
simple example. Suppose two persons go to a library, library has all the books but two persons
will read different books depending on their need. In this example DNA in the nucleus can be
understood as our library and segments of DNA that are genes can be compared with books in
that library, while cells i.e. muscle, skin, nerve cells etc. they can be thought as reading different
books in the same DNA library.

 Mechanism of differentiation:-

Genes give information about proteins, which makes cells different from each other that’s why
muscle cells act differently from skin cells. As all cells are being formed from the same stem
cells which has all the genes, so for a specific cell ,genes of that cells are “turned on” means
expressed while all other genes are “turned off” i.e. they are not expressed. For example for
muscle cells, stem cells will turn on muscle cell genes and will turn off all other genes.

 Cues for differentiation:-

There are certain cues on the basis of which some genes are turned off and some are turned on.

These cues can be:-

 Internal
 External

Certain chemicals or molecules present in the surrounding of cells may interact with them,
causing them to differentiate.

These external signals can be passed in the following ways:-

1- Diffusion:-

Signals released by one group of cells may simply diffuse to the nearby group of cells and then
bind on their receptors.

2- Direct Contact:-

There may be a direct contact between the two group of cells, it occurs through surface proteins.

3-Gap Junction:-

Connexons proteins present in the gap between cells forms gap junctions and signals for cell
differentiation can be conducted by these gap junctions.
  Importance of induction:-

Induction causes formation of limbs, ears, eyes and many other body parts.

 Sources of embryonic type stem cells:

 Embryos-Embryonic stem cells are obtained by harvesting living embryo which are
generally 5_7 days old. The removal of embryonic stem cells invariably results in
the destruction of the embryo..

Experimental evidences in favor of potency of Embryo blasts:

In an experiment, cells from embryoblast of a white colored albino mouse were taken and were
introduced into the blastocyst of a black skin coat color mouse, the off springs produced had
white and black patches on the skin coat and it was also possible to study that which parts of the
body of mouse were formed by its own embryonic stem cells and which of the parts were formed
by the embryonic cells of the host. This type of experiments shows that embryoblast cells can
give rise to all cells of the body.

 Hayashi’s researchers group in Japan practically demonstrated that embryonic stem cells
of mouse could produce primordial germ cells, which can give rise to sperm and egg cells
and these can also be incorporated into a mature individual by transferring them to
gonads of mouse.
  A chimeric mouse produced at Vanderbilt University in Nashville, Tennessee, source:
Stamcellen Veen Magazines

Sources of adult type stem cells:

 Umbilical cords, Placentas and Amniotic fluid- adult type stem cells can be derived from
various pregnancies-related tissues.
 Adult tissues-In adults, stem cells are present within the bone marrow, liver, epidermis,
retina,skeltal muscles, intestine, brain and elsewhere.
  Comparison of embryonic and adult stem cells:
 Advantages of embryonic stem cell:
i. Flexible_ appear to have the potentialto make any cell.
ii. Immortal_ one embryonic stem cell line can provide an endless supply of cells
with defined characteristics.
iii. Availability_ embryos from in vitrofertillization clinics.
 Disadvantages of embryonic stem cells:
i. Difficult to differentiate uniformly and homogenously into a target tissues.
ii. Immunogenic_ embryonic stem cells from a random embryo donor are
likely to be rejected after transplantation
iii. Tumorigenic_ capable of forming tumors or promoting tumor formation.
 Advantages of adult stem cells:
i. Adult stem cells from bone marrow and umbilical cord appear to be as
flexible as the embryonic type.
ii. Not immunogenic recipients who receive the product of their own stem
cells will not experience immune rejection.
iii. Non tumorigenic_tend not to form tumors.
 Disadvantages of Adult stem cells:
i. Limited quantity_ can sometime be difficult to obtain in large numbers.
ii. Finite_ may not live as long as embryonic stem cells in culture.
iii. Less flexible_ may be more difficult to reprogram to form other tissue
types.
 Classification of stem cells on the level of differentiation:
1) Totipotent stem cells.
2) Pluripotent stem cells.
3) Multipotent stem cells.
4) Unipotent stem cells.
1. Totipotent stem cells:

These can produce any type of cell .cells of zygote are Totipotent and can differentiate into about
220 type of cells of embryo and also of placenta. It supports embryonic developmend in utero.
 2. Pluripotent stem cells:
 Pluripotent stem cells are the descendents of totipotent stem cells of the
embryo.
 These cells develop about four days after fertilization.
 They can differentiate into any cell type.

Thus, pluripotent cells have the potential to give rise to any type of cell.

 These cells can recreate a complete organism but differentiate to a large

number of mature tissue types, for example brain and muscle.
 3. Multipotent stem cells: are descendents of pluripotent stem cells antecendents of
specialized cells in particular tissues.

For example; Hematopoietic stem cells ,which are found primarily in the bone marrow , give
rise to all of the cells found in the blood, including red blood cells, white blood cells & platelets.
 4. Unipotent stem cells:
 Unipotent stem cell, a term that is usually applied to a cell in adult organisms, means that
the cells in question are capable of differentiating along only one lineage.
 “uni”is derived from latin word unus,which means one.
 Progenitor cells or( unipotent stem cells) can produce only one cell type.
 For example; erythroid progenitor cells differentiate into only red blood cells.

 Stem cell therapies:-

1- Wounds or burns of skin heal due to renewal of stem cells of skin. Skin adult stem cells
produce more cells. In lab multipotent stem cells of skin can be changed into pluripotent
stem cells and pluripotent stem cells can be used to produce skin cells like keratinocytes,
these cells of skin give rise to many other cellular components.

I-stem is a research institute in France, its goal is to produce skin from skin stem cells of adult,
so that skin can be available for the patients having skin injuries.
In a research that was conducted by scientists at NYU School of medicines, it was showed that
in diabetic patients wounded skin can be healed by giving injections that has stem cells derived
from bone marrow, and the healing rate is almost 50 percent more. The signaling pathway of the
cell is damaged in diabetes, the stem cells that are injected, repair this signaling pathway.

2- Hematopoietic stem cells transplantation can cure many blood diseases. For example
leukemia, a cancer of blood can also be cured by it.

Through chemotherapy, abnormal cells killers are induced in the patient, due to which abnormal
hematopoietic stem cells are destroyed and then healthy hematopoietic stem cells are introduced
in the body which forms new cells. Donor hematopoietic stem cells may be taken from the blood
released with placenta during child birth.

3- Mesenchyme stem cells are present in the connective tissues which surrounds the organs of
the body. In 2013, researchers of Massachusetts General Hospital in PNAS early edition
said that by using stem cells of humans, blood vessels of mice can be produced.

These blood vessels were produced in mice within 2 weeks after the induction of stem cells of
humans.

4- After damage, liver can be repaired due to stem cells.

5- In vitro fertilization (IVF) is the procedure in which sperms and eggs are fertilized outside
the body, in a test tube and when this fertilized egg reaches blastocyst stage then it is
transferred to the mother’s womb. Louise Brown was the first baby born in 1978 by IVF
process.

During IVF, many eggs and sperms of a couple are fertilized, as only one embryo is implanted
into the mother, the remaining embryos are surplus, these can be used for the other couples who
are unable to have children. These extra embryos are used for Human embryonic stem cell
lines. First embryonic stem cell line was created by an American scientist James Thompson
in 1998.

Presently there are about 400,000 IVF produced embryos in US, these can be used for the
treatment of infertility but former President Bush in August 2001, banned the government
funding on human embryonic stem cell lines. But many other countries like China, Spain,
Israel, Korea and Australia etc. allow the derivation of human embryonic stem cells.

6- These cells are then grown in the laboratory and when there number increases, then the
damaged cornea is removed and the limbal stem cells grown in the laboratory are implanted
around the iris of patient, these stem cells begin to produce different layers of cornea, patient
recovers vision within few months.

1- STEM CELL TECHNOLOGIES:

1- Muscle stem cell technology
2- Induced pluripotent stem cell technology
3- Human embryonic stem cell technology

1) MUSCLE STEM CELL TECHNOLOGY:

 Scientists at UMASS chan Medical School have developed a technology to isolate human
skeletal muscle stem cells,or progenitor cells,from induced pluripotent stem cells.
 Patient- derived stem cell, such as iMyoblast,are a core foundation for preclinical
laboratory models for many known human muscular dystrophies.
 There are 40 known muscular dystrophies caused by genetic mutations that affect muscle
function.
 These disorders have variable ages of onset and clinical severity ,but most often result in
severe physical disabilities and premature death.
 Patients with muscular dystrophy experience progressive muscle weakness and decreased
mobility making everyday task difficult and often imposible to perform even during
early disease.
 The primary benefit of iMyoblast is their ability to regenerate to create more progenitor
cells in addition to differentiating into mature muscle cells.these early technologies are
limited in their ability to make muscle stem cells that can both differentiate and
regenerate muscles.
 In contrast ,skin cells taken from a patient with any form of muscular dystrophy can be
turned into iMyoblast progenitor cells when iMyoblast are then engrafted into animal
models ,they give rise to adult human muscle cells with muscular dystrophy causing
mutation. These disease models are key to developing new therapeutics with the potential
to treat muscular dystrophies.
 The long –term goal is that we can develop gene editing technology to fix the disease-
causing mutations in the iMyoblast,which can then be transplanted back into the patients
where they go to build healthy muscle tissues.

2- INDUCED PLURIPOTENT STEM CELL TECHNOLOGY:

Induced pluripotent stem cells are derived from skin or blood cells that have
been reprogrammed back into an embryonic –like pluripotent state that enable the
development of an unlimited source of any type of human cell needed for therapeutic
purposes.
FOR EXAMPLE induced pluripotent stem cell can be prodded into becoming beta islet
cells to treat diabetes , blood cell to create new blood free of cancer cells for a leukemia
patients ,or neuron to treat neurological disorders.
 In late 2007, a BSCRC team (Broad stem cell research center) team of faculty ,Kathrin
Plath,William Lowry,Amander Clark and April Pyle were among the first to create
human induced pluripotent stem cell .
 Using iPSC technology our faculty have reprogrammed skin cells into active motor
neurons, egg and sperm precursors, and blood cells.
 In addition patients with untreated diseases such as ALS (Amyotrophic lateral
sclerosis),rett syndrome and Duchenne’s Muscular dystrophy donate skin cells to
BSCRC scientists for iPSC reprogramming research .
 The generous participation of patients and their families in this research enable BSCRC
scientists to study these diseases in the laboratory in the hope if developing new
treatment technologies.
3- HUMAN EMBRYONIC STEM CELL TECHNOLOGY :
 Human embryonic stem cell research is a new technology that provides new insights
into cause of disease and the development of effective therapies.
 Research on stem cell is increasing our understanding about how organ develop
normally from single cell and also about how healthy cells can replace those that are
damaged by disease.
 Embryonic stem unique in their ability to renew themselves indefinitely by
producing identical cells .in addition ,under certain physiological and experimental
conditions ,they can be induced to give rise to many different type of cells each with
specialized function
 Embryonic stem cell technology has a potential to treat conditions such as
diabetes ,parkinson’s disease,and spinal cord injury
 Human embryonic stem cells (hESCs) also represent new technologies for research
and development and canbe used for drug screening and testing ,drug toxicology
studies as well as new drug target investigation .
 Future research on human embryonic stem cell lines:- These can provide material for
testing of drugs on human tissues, which is otherwise not possible.
 For example drugs for human heart diseases are tested on animals only and can’t be
tested on human’s heart tissues.