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INTRODUCTION
 A stem cell is essentially the building block of the
human body. The stem cells inside an embryo will
eventually give rise to every cell, organ and tissue in
the fetus's body. Unlike a regular cell, which can only
replicate to create more of its own kind of cell, a stem
cell is pluripotent. When it divides, it can make any
one of the 220 different cells in the human body.
Stem cells also have the capability to self-renewal
they can reproduce themselves many times .

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 HISTORY
 1960s - Joseph Altman and Gopal Das present scientific
evidence of adult neurogenesis, ongoing stem cell
activity in the brain; their reports contradict Cajal's "no
new neurons" dogma and are largely ignored.

 1963 - McCulloch and Till illustrate the presence of

self-renewing cells in mouse bone marrow.

 1968 - Bone marrow transplant between two siblings

successfully treats chronic ischemic disease
 1978 - Haematopoietic stem cells are discovered in
human cord blood. 3
 1981 - Mouse embryonic stem cells are derived from the
inner cell mass by scientists Martin Evans, Matthew Kaufman,
and Gail R. Martin. Gail Martin is attributed for coining the
term "Embryonic Stem Cell".

 1992 - Neural stem cells are cultured in vitro as neurospheres.

 1997 - Leukemia is shown to originate from a haematopoietic

stem cell, the first direct evidence for cancer stem cells.

 1998 - James Thomson and coworkers derive the first human

embryonic stem cell line at the
University of Wisconsin-Madison.

 2000s - Several reports of adult stem cell plasticity are

published.

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 2001 - Scientists at Advanced Cell Technology clone
first early (four- to six-cell stage) human embryos for
the purpose of generating embryonic stem cells.

 2003 - Dr. Songtao Shi of National Institute of Health

discovers new source of adult stem cells in children's
primary teeth.

 2004-2005 - Korean researcher Hwang Woo-Suk

claims to have created several human
embryonic stem cell lines from unfertilised human
oocytes. The lines were later shown to be fabricated.
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 2005 - Researchers at Kingston University in England
claim to have discovered a third category of stem cell,
dubbed cord-blood-derived embryonic-like stem cells
(CBEs), derived from umbilical cord blood. The
group claims these cells are able to differentiate into
more types of tissue than adult stem cells.

 August 2006 - Rat Induced pluripotent stem cells:

the journal Cell publishes Kazutoshi Takahashi and
Shinya Yamanaka,
"Induction of Pluripotent Stem Cells from Mouse Em
bryonic and Adult Fibroblast Cultures by Defined Fac
tors"
.

 October 2006 - Scientists in England create the first

ever artificial liver cells using umbilical cord blood 6
stem cells.
 January 2007 - Scientists at Wake Forest University led by
Dr. Anthony Atala and Harvard University report discovery of
a new type of stem cell in amniotic fluid.This may potentially
provide an alternative to embryonic stem cells for use in
research and therapy.

 June 2007 - Research reported by three different groups

shows that normal skin cells can be reprogrammed to an
embryonic state in mice. In the same month, scientist
Shoukhrat Mitalipov reports the first successful creation of a
primate stem cell line through somatic cell nuclear transfer]

 October 2007 - Mario Capecchi, Martin Evans, and

Oliver Smithies win the 2007
Nobel Prize for Physiology or Medicine for their work on
embryonic stem cells from mice using gene targeting
strategies producing genetically engineered mice (known as
knockout mice) for gene research.
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 November 2007 - Human Induced pluripotent stem cells: Two
similar papers released by their respective journals prior to formal
publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka,
"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts
by Defined Factors"
, and in Science by Junying Yu, et al., from the research group of
James Thomson,
"Induced Pluripotent Stem Cell Lines Derived from Human Somatic
Cells"
: pluripotent stem cells generated from mature human fibroblasts. It
is possible now to produce a stem cell from almost any other human
cell instead of using embryos as needed previously, although the
risk of tumorigenesis due to c-myc and retroviral gene transfer
remains to be determined.

 January 2008 - Human embryonic stem cell lines were generated

without destruction of the embryo[38]

 January 2008 - Development of human cloned blastocysts 8

following somatic cell nuclear transfer with adult fibroblasts[39]
 TYPES OF STEM CELL
 There are two types of stem cells: embryonic
stem cells and adult stem cells. Embryonic
stem cells come from an embryo –
 The mass of cells in the earliest stage of
human development that, if implanted in a
woman's womb, will eventually grow into a
fetus. When the embryo is between three and
five days old, it contains stem cells, which are
busily working to create the various organs
and tissues that will make up the fetus
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 Adults also have stem cells in the heart, brain,
bone marrow, lungs and other organs. They are
our built-in repair kits, regenerating cells
damaged by disease, injury and everyday wear
and tear. Adult stem cells were once believed to
be more limited than stem cells, only giving rise
to the same type of tissue from which they
originated. But new research suggests that adult
stem cells may have the potential to generate
other types of cells, as well. For example, liver
cells may be coaxed to produce insulin, which is
normally made by the pancreas. This capability
is known as plasticity or transdifferentiation 10
 While embryonic stem cell potential remains
untested, adult stem cell treatments have been used
for many years to treat successfully leukemia and
related bone/blood cancers through bone marrow
transplants.[19] The use of adult stem cells in
research and therapy is not as controversial as
embryonic stem cells, because the production of adult
stem cells does not require the destruction of an
embryo. Consequently, more US government funding
is being provided for adult stem cell research.[
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 cord blood ( placental) stem cells
 The umbilical cord and placenta are fully-
developed organs and are a source of one or
two types of limited (adult) stem cells, the
blood producing stem cell and perhaps some
connective tissue cells. Upon giving birth, it is
possible to save or donate these stem cells for
potential transplants to treat blood diseases in
small children or donate them for research.

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PROPERTIES OF STEM CELL
 The classical definition
of a stem cell requires
that it possess two
properties:
 Self-renewal - the
ability to go through
numerous cycles of
cell division while
maintaining the
undifferentiated state.
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 Potency - the capacity to differentiate into
specialized cell types. In the strictest sense,
this requires stem cells to be either totipotent
or pluripotent - to be able to give rise to any
mature cell type, although multipotent or
unipotent progenitor cells are sometimes
referred to as stem cells.

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 Potency specifies the differentiation potential (the potential to
differentiate into different cell types) of the stem cell.
 Totipotent stem cells are produced from the fusion of an egg
and sperm cell. Cells produced by the first few divisions of the
fertilized egg are also totipotent. These cells can differentiate
into embryonic and extraembryonic cell types.
 Pluripotent stem cells are the a variety of totipotent cells and
can differentiate into cells derived from any of the three
germ layers.
 Multipotent stem cells can produce only cells of a closely
related family of cells (e.g. hematopoietic stem cells
differentiate into red blood cells, white blood cells, platelets,
etc.).
 Unipotent cells can produce only one cell type, but have the
property of self-renewal which distinguishes them from non-
stem cells (e.g. muscle stem cells).
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 HOW THEY WORK
 Stem cell division and 1
differentiation. A -
stem cell; B - progenitor
cell; C - differentiated 2
cell; 1 - symmetric stem
cell division; 2 - 3
asymmetric stem cell
division; 3 - progenitor
division; 4 - terminal 4
differentiation
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 To ensure self-renewal, stem cells undergo
two types of cell division (see Stem cell
division and differentiation diagram).
Symmetric division gives rise to two identical
daughter cells both having stem cell
properties. Asymmetric division, on the other
hand, produces only one stem cell and a
progenitor cell with limited self-renewal
potential. Progenitors can go through several
rounds of cell division before terminally
differentiating into a mature cell.
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 An alternative theory is that stem cells remain undifferentiated
due to environmental cues in their particular niche. Stem cells
differentiate when they leave that niche or no longer receive
those signals. Studies in Drosophila have identified the
signals dpp and junctions that prevent germarium stem cells
from differentiating.

 The signals that lead to reprogramming of cells to an

embryonic-like state are also being investigated. These signal
pathways include several transcription factors including the
oncogene c-Myc. Initial studies indicate that transformation of
mice cells with a combination of these anti-differentiation
signals can reverse differentiation and may allow adult cells to
become pluripotent. However, the need to transform these
cells with an oncogene may prevent the use of this approach in
therapy.
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 Controversy surrounding human
embryonic stem cell research
 There exists a widespread controversy over
human embryonic stem cell research that
emanates from the techniques used in the
creation and usage of stem cells.
Human embryonic stem cell research is
controversial because, with the present state of
technology, starting a stem cell line requires
the destruction of a human embryo and/or
therapeutic cloning.
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 However, recently, it has been shown in principle that
embryonic stem cell lines can be generated using a
single-cell biopsy similar to that used in
preimplantation genetic diagnosis that may allow
stem cell creation without embryonic destruction.

 It is not the entire field of stem cell research, but the

specific field of human embryonic stem cell research
that is at the centre of an ethical debate.

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 Opponents of the research argue that embryonic stem
cell technologies are a slippery slope to reproductive
cloning and can fundamentally devalue human life.
Those in the pro-life movement argue that a human
embryo is a human life and is therefore entitled to
protection.
 Contrarily, supporters of embryonic stem cell
research argue that such research should be pursued
because the resultant treatments could have
significant medical potential. It is also noted that
excess embryos created for in vitro fertilisation could
be donated with consent and used for the research.

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 Therapeutic cloning or somatic cell
nuclear transfer (SCNT)
 Somatic cell nuclear transfer (SCNT) involves
transplanting a patient's genetic material from
something as simple as a skin cell into an unfertilized
egg in order to grow patient specific stem cells.
 No sperm is involved, and therefore no fertilization
occurs, in this procedure. Also, because the group of
cells from which the stem cells are derived are not
implanted in a uterus, no fetus is involved.

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 There is a big difference between reproductive
cloning and therapeutic cloning.
 Reproductive cloning involves creating an embryo
and then actually implanting it into a uterus. It is
highly unlikely this could work for humans, and for
ethical and scientific reasons, all but a handful of
radical scientists are strongly opposed to attempting
it. Therapeutic cloning creates an embryo but never
implants this in a uterus as it intends to only create
patient specific stem cells, not a person.
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 SCNT has promise for therapies because the stem
cells have identical DNA to the patient, thereby
avoiding problems of rejection by the patient's body.
SCNT is also a critical tool to create disease-specific
cell lines that can be studied in vitro (outside the
body) to learn how complex diseases develop and to
understand how certain drugs may affect the
progression of that disease. The technique has been
proven to work in animal cells but has not yet been
proven in human cells.

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 SUMMERY
 After twenty years of research, there are no approved
treatments or human trials using embryonic stem cells. ES
cells, being totipotent cells, require specific signals for correct
differentiation - if injected directly into the body, ES cells will
differentiate into many different types of cells, causing a
teratoma. Differentiating ES cells into usable cells while
avoiding transplant rejection are just a few of the hurdles that
embryonic stem cell researchers still face. Many nations
currently have moratoria on either ES cell research or the
production of new ES cell lines. Because of their combined
abilities of unlimited expansion and pluripotency, embryonic
stem cells remain a theoretically potential source for
regenerative medicine and tissue replacement after injury or
disease.

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 Microscopic 10x view
of a colony of
embryonic stem cells
(The stem cell colonies
are the rounded, dense
masses of cells.)

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 Amniotic fluid yields stem cells,
Harvard researchers report
 It's the latest advance in the so-called regenerative medicine
field that has sprung from Atala's lab in Winston-Salem, N.C.
In April, Atala and his colleagues rebuilt bladders for seven
young patients using live tissue grown in the lab.
 In the latest work, Atala's team extracted a small number of
stem cells swimming among the many other cell types in the
amniotic fluid. One of the more promising aspects of the
research is that some of the DNA of the amnio stem cells
contained Y chromosomes, which means the cells came from
the babies rather than the pregnant moms.

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Cells Discarded From Womb Lining
During A Woman's Period Are New
Type Of Stem Cell
 ScienceDaily (Nov. 16,
2007) — The cells
which thicken the womb
wall during a woman's
menstrual cycle contain
a newly discovered type
of stem cell, and could
be used in the treatment
of damaged and/or old
tissue, according to new
research.
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 A) Morphology of freshly isolated
menstrual blood mononuclear
cells. B) Fibroblast-like
morphology of menstrual blood
mononuclear cells after 2-week
cell culture. C) Clonal population
of menstrual cells after plating in
96 well plate 1 week after cloning.
D) The same population 2 weeks
after cloning. (Credit: Image
courtesy of BioMed Central)

Article: Xiaolong Meng, Thomas E

Ichim, Jie Zhong, Andrea Rogers,
Zhenglian Yin, James Jackson, Hao
Wang, Wei Ge, Vladimir Bogin,
Kyle W Chan, Bernard Thebaud
and Neil H Riordan, "Endometrial
regenerative cells: A novel stem
cell population"  Journal of
Translational Medicine (in press)
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 Stem Cells Train Heart Following
Heart Attack
 ScienceDaily (Nov. 30,
2007) — Injecting adult
stem cells into a heart
following a heart attack
(infarction) improves the
heart function and
strengthens the heart wall.
The use of such cells may
eventually reduce the
chance of heart failure
following a heart attack.
 Adapted from materials
provided by Netherlands
Organization for Scientific
Research. 30
 Adult Cells, Reprogrammed To Embryonic
Stem Cell Like State, Treat Sickle-cell
Anemia In Mice
 ScienceDaily (Dec. 7, 2007)
— Mice with a human sickle-
cell anemia disease trait have
been treated successfully in a
process that begins by directly
reprogramming their own
cells to an embryonic-stem-
cell-like state, without the use
of eggs. This is the first proof-
of-principle of therapeutic
application in mice of directly
reprogrammed "induced
pluripotent stem" (IPS) cells,
which recently have been
derived in mice as well as
humans.
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 New Way To Sort Stem Cells
Discovered
 ScienceDaily (Dec. 29, 2007) —
The method uses electrodes on a
tiny, inch-long glass slide to sort
cells by their electric charges and
has been used in cancer research.
The stem cell field suffers from a
lack of tools for identifying and
sorting cells. This important
discovery could add a new tool to
current sorting methods, which
generally require expensive,
bulky equipment.

Adapted from materials provided

by University of California -
Irvine.
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 Human Embryonic Stem Cell Lines Created
Without The Destruction Of Embryos
 ScienceDaily (Jan. 12, 2008) —
Single cells were removed from the
embryos using a technique similar to
preimplantation genetic diagnosis
(PGD). The biopsied embryos
continued to develop normally and
were then frozen. The cells that were
removed were cultured utilizing a
proprietary methodology that
recreates the optimal developmental
environment, which substantially
improved the efficiency of deriving
stem cells to rates comparable to
using the traditional approach of
deriving stem cells from the inner cell
mass of a whole blastocyst stage
embryo.

Journal article summary is

available at
:http://www.cellstemcell.com/con 33
tent/article/
 Cloned Human Embryo Created
From Skin Cells
 ScienceDaily (Jan. 22, 2008)
— Stemagen, a privately
held embryonic stem cell
research company,
announced January 17 it has
become the first in the world
to create, and meticulously
document, a cloned human
embryo using somatic cell
nuclear transfer (SCNT).

 Adapted from materials

provided by Stemagen.
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 Hybrid Human-Animal Embryo
Research Approved In The UK
 ScienceDaily (Jan. 18,
2008) — Two research
groups in the United
Kingdom have been given
permission to use hybrid
human-animal embryos in
research which aims to lead
to the development of new
therapies for debilitating
human conditions such as
Parkinson’s disease and
stroke.

 http://www.hfea.gov.uk/en/
1640.html
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 Stem Cell Treatment For Brittle
Bones In The Womb
 ScienceDaily (Jan. 30, 2008) —
The extraordinary results of an in
utero stem cell treatment could
lead to a new treatment for babies
with brittle bones, as well as a
range of other disabling
conditions, according to a
maternal-fetal medicine
researcher, now based at The
University of Queensland (UQ).

 Adapted from materials provided

by University of Queensland.

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 Bone Marrow Stem Cell Release Regulated
By Brain's Biological Clock
 ScienceDaily (Feb. 7, 2008) —
Mount Sinai researchers have
discovered that the release of
blood stem cells from bone
marrow is regulated by the brain
through the cyclical human
biological clock, via adrenergic
signals transmitted by the
sympathetic nervous system.
These new findings point out that
the harvest of stem cells for
transplantation may be improved
by timing it at the peak of their
release
 This research was published
online February 6 on the website
of the journal Nature.
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 Stem Cell Lines Created From Poor Quality
Embryos Discarded From Fertility Clinics
 cienceDaily (Jan. 31, 2008) —
Human embryos that are
discarded every day as medical
waste from in vitro fertilization
(IVF) clinics could be an
important source of stem cells for
research, according to a team of
researchers at Children's Hospital
Boston. Some of the embryos
created during IVF are deemed
"clinically useless" because of
imperfections, but a paper
published in the January 27 online
edition of Nature Biotechnology
shows that it is possible to derive
stem cell lines from these poor-
quality embryos.
Adapted from materials provided
by Children's Hospital Boston 38
 Stem Cells and Aging
 a recent study, which used blood cells precursors
called hematopoietic stem cells, found that our genes
that are active in responses to stress and inflammation
become more active as we age but the genes that
regulate the gene expression itself become less active.
As we age, it’s believed that inflammation increases
throughout the body, especially in areas like the
arteries, brain and kidneys. This means that these
stem cells, just like other cells in our bodies, are
susceptible to the degradation that comes with age,
which helps us to better understand the dynamics of
the aging process.
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 Breast milk contains stem cells
Monday, 11 February 2008
 The Perth scientist who
made the world-first
discovery that human breast
milk contains stem cells is
confident that within five
years scientists will be
harvesting them to research
treatment for conditions as
far-reaching as spinal
injuries, diabetes and
Parkinson’s disease.

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For over 30 years stem cells have been used to treat patients with
conditions such as leukemia and lymphoma. Stem cells are
used in the treatment of a wide range of conditions today with
positive and encouraging results.
The following diseases have been treated by various stem cell
practitioners with generally positive results:
• Autism
• Cerebral Palsy
• Diabetes Type II
• Heart Disease
• Multiple Sclerosis
• Parkinson's Disease
• Rheumatoid Arthritis
• Stroke
• Inflammatory Bowel Disease
• Anti-ageing
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Bioengineered Teeth from Cultured
Rat Tooth Bud Cells
 Analyses of 12-week implant tissues demonstrated
that dissociated 4-dpn rat tooth bud cells seeded for 1
hr onto PGA or PLGA scaffolds generated
bioengineered tooth tissues most reliably. We
conclude that tooth-tissue-engineering methods can
be used to generate both pig and rat tooth tissues.
Furthermore, our ability to bioengineer tooth
structures from cultured tooth bud cells suggests that
dental epithelial and mesenchymal stem cells can be
maintained in vitro for at least 6 days
 M.T. Duailibi et al

 J Dent Res 83(7): 523-528, 2004

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 Hard Tissue Formation in Subcutaneously
Transplanted Rat Dental Pulp
 we evaluated hard tissue induced by transplantation
of pulp into subcutaneous tissue. Seven days after
transplantation, initial hard tissue was formed at the
inner periphery of the pulp. After 14 days, this hard
tissue expanded inwardly. Mineralized matrix was
immunopositive for osteocalcin, osteopontin, and
bone sialoprotein, but negative for dentin
sialoprotein.
 A. Hosoyaet al

 J Dent Res 86(5):469-474, 2007

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 Stem cells in tooth pulp could be
used in research
 Researchers from the United States and
Australia have found that deciduous teeth have
robust stem cells in their dental pulp. The
finding is important, because such teeth may
serve as an easily obtainable alternative to
embryonic stem cells, the use of which has
proved controversial.
 Nebraska Deborah Josefson

 BMJ 2003;326:950 ( 3 May )

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 Banking Baby, Wisdom Teeth For
Stem Cells
 NEW YORK, June 8, 2005—Baby and wisdom teeth,
along with jawbone and periodontal ligament, are
non-controversial sources of stem cells that could be
"banked" for future health needs, according to a
National Institutes of Health researcher who spoke
today at the American Dental Association's national
media conference.

Contact Information:
Telephone: 312-440-2806
E-mail: mediarelations@ada.org (Journalists) or Contact ADA
(All Others)
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 The use of adult stem cells in
rebuilding the human face
 BMSCs have the potential to re-create tissues of the
craniofacial region to restore normal structure and
function in reconstructing the hard tissues of a face.
Ex vivo expanded BMSCs with scaffolds have been
used in a limited number of patients to date, but likely
will be used more extensively in the near future.
 Pamela Gehron Robey

 J Am Dent Assoc, Vol 137, No 7, 961-972. 2006

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 Dental pulp stem cells (DPSCs) and bone
marrow stromal stem cells (BMSSCs), which
can differentiate into multiple mesenchymal
cell lineages, are putative candidate cells for
tooth and bone tissue engineering respectively
(Gronthos et al., 2000; Bianco et al., 2001;
Gronthos et al., 2002; Batouli et al., 2003;
Gronthos et al., 2006; Yeon Lim et al., 2006).

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