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Stem Cells

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Stem Cells Americans Following the Issue of Stem Cell Research Americans Favor Embryonic Stem Cell Research (ESCR) ESCR Policy Should Be Nationally Uniform Majority ... – PowerPoint PPT presentation

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Title: Stem Cells


1
Stem Cells
2
What is a Stem Cell? In general a stem cell
is A cell that can divide indefinitely A
self-replicating cell A cell that can produce
the differentiated cells required for functional
tissues given the right conditions given
the right signals
3
Classification of Human Stem Cells
Human Stem Cells
Embryonic Stem Cells
Fetal Stem Cells
Infant
Adult
Umbilical Cord Blood Stem Cells
A. Bongso and E.H. Lee, Stem Cells from Bench
to Bedside, World Scientific Publishing Co. Pte.
Ltd., 2005
4
Potential of Stem Cells Totipotent can
produce all the cells in the embryo and the
embryos contribution to the extra-embryonic
tissues Pluripotent can produce all the cell
types in the embryo Proper Multipotent
contributes cells to several cell
lineages (Adapted from Wagers and Weissman,
Cell 116639-648, 2004)
5
Totipotency and pluripotency Embryonic cells up
to the blastomere stage are considered to be
totipotent because one cell can make all of the
embryonic and extraembryonic cells. Cells of the
inner cell mass of the blastocyst are considered
to be pluripotent because one cell can contribute
to all cells and tissues in a whole organism.
Embryonic stem cells (ES cells) are derived from
cells of the inner cell mass. Pluripotency of ES
cells was shown by making chimeric mice.
6
making chimeric mice.
7
What is Multipotency? Multipotency is
defined as The stem cell itself changing its
phenotype The stem cell produce progeny with
phenotypes and functions different than its
own in response to changes in the stem cell
niche factors added to cultures new
signals in vivo Somatic stem cells from most
tissues are now thought to be multipotent.
8
Examples of Multipotency of Some Somatic Stem
Cells Type of Stem Cell Type of Cells/Tissue
Generated 1. Mesenchymal 1. Keratinocytes,
mesenchymal cells, muscle, blood 2. Epidermal 2.
Keratinocytes, fibroblasts, endothelial, brain,
blood cells, sebaceous 3. Neural 3. Neurons,
oligodendrocytes, skeletal muscle,
blood cells 4. Bone Marrow 4. Blood cells,
endothelial, cartilage, bone, dermis, liver,
adipocytes, gastrointestinal, thymus,
pulmonary epithelial, islet cells 5.
Muscle/satellite 5. Skeletal muscle, bone,
cartilage, fat, smooth muscle, cardiac
muscle 6. Oval Liver Cells 6. Hepatocytes,
blood cells 7. Testis Ovarian 7. Gonads,
mesenchymal cells 8. Pancreatic Acinar 8. Islet
cells 9. Adipocytic 9. Fat, muscle, cartilage,
bone
9
Why are Multipotent Somatic Stem Cells
Important? 1. The use of embryonic stem cells
has legal and ethical problems. Cells from the
patient who requires the new tissue will
not have legal or ethical problems. 2.
Embryonic stem cells potentially carry MHC
markers that may cause rejection of tissues made
with these cells. There should be no rejection
problems if the patients own cells are
used. 3. Injection of embryonic stem cells has
been shown to cause benign tumors, called
teratomas, which contain differentiated cells of
all the tissues, such as bone, teeth, muscle,
etc. Injection of normal somatic cells have
not caused the formation of benign or malignant
tumors
10
What are Embryonic Stem Cells? Embryonic stem
cells (ES cells) are derived from the cells in
the inner cell mass of the developing blastocyst
Most ES cell work is done with murine ES
cells Human ES cells are derived from embryos
that developed from eggs that were fertilized in
vitro in an in vitro fertilization clinic They
have been donated for research with informed
consent of the donors. Human ES cells are not
derived from eggs fertilized in a woman's body.
11
Embryonic Stem (ES) Cells Culture of ES Cells
ES cells can be isolated and maintained in
culture Fibroblast feeder layer (STO cells or
MEF cells) LIF (leukocyte inhibitory factor)
for mouse ES cells LIF is not required for
human ES cells Differentiation of ES Cells
Cultured ES cells can be induced to differentiate
into multiple tissues by addition of specific
cytokines or growth factors to the culture
medium. Once differentiated, ES cells are
no longer pluripotent
12
Three types of cultured embryonic cells can form
normal offspring ES cells EG cells EC cells
13
(No Transcript)
14
What are Somatic Stem Cells (adult stem
cells)? Somatic stem cells are
undifferentiated cells found in a tissue, such as
the skin or the brain sometimes called tissue
stem cells or adult stem cells, even though they
are also found in neonatal and embryonic
tissues located among differentiated cells in a
tissue or organ Somatic stem cells can renew
themselves indefinitely in vivo The primary
role of somatic stem cells is to produce
the differentiated cells for maintenance and
repair the tissue in which they reside The
origin of somatic stem cells in mature tissues is
unknown There is evidence that they are defined
by their environmental niche
15
Adult Stem Cells
- Bone Marrow Stem Cells - Peripheral Blood Stem
Cells - Neuronal Stem Cells (from olfactory bulb,
spinal cord) - Muscle Stem Cells - Liver Stem
Cells - Pancreatic Stem Cells - Corneal Limbal
Stem Cells - Umbilical Cord Blood
16
Hematopoietic stem cells were the first somatic
stem cells functionally identified
Hematopoietic stem cells were the first somatic
stem cells to be identified. In 1961 Till and
McCullough determined that after irradiation only
a few cells repopulated the spleen. (Radiat. Res.
14 213-219,1961). Found in the bone marrow,
these stem cells can be induced to differentiate
into all functional blood cells (lymphocytes,
erythrocytes, megakaryocytes, monocytes,
granulocytes, etc.)
17
Hematopoietic stem cells
18
Patterns of stem cell division Symmetric cell
division results in two equal daughter cells.
This is how ES cells reproduce. During
development or under repair circumstances,
somatic stem cells may also reproduce by
symmetric cell division. Asymmetric cell
division results in two daughter cells with
different potential. It is thought that somatic
stem cells have asymmetric cell
division, producing one daughter cell that
remains a stem cell and one daughter cell that is
committed to differentiate. ES cells may show
asymmetric cell division when producing committed
cells. Committed progenitor cells may show
symmetric cell division for a specific number of
cell cycles, producing several cells with equal
potential.
19
Patterns of stem cell division
20
Stem cell Niche Both ES cells and somatic
stem cells are thought to be maintained (and
perhaps defined) by the environment produced by
the surrounding differentiated cells. Exactly
how this stem cell niche is maintained is not
known yet. The differentiated cells may
secret specific factors into the surrounding
matrix communicate with the stem cells via gap
junctions or receptor mediated inducers Such
communication may activate specific signaling
pathways, such as the Wnt/frizzled (which
activates Lef-1/TCF), Notch/delta, or Sonic
hedgehog/patched pathways. Loss of the stem
cell niche can induce a stem cell to divide, die,
or differentiate. Change in the niche may
induce a stem cell to alter its phenotype and its
function.
21
Stem cell Niche
22
Summary Embryonic vs. Somatic Stem
Cells Embryonic Stem Cells Somatic Stem
Cells Called ES cells Also called adult
stem cells Derived from the inner cell mass of
Derived from a specific tissue, such the
developing blastocyst as the epidermis High
plasticity and developmental Developmental
potential uncertain potential Unlimited
lifespan in culture Limited lifespan in
culture Limited lifespan in vivo May have
unlimited lifespan in tissues May be
rejected due to allogeneinc High potential for
autologous grafts nature Potential for
undesired tumor Less likely to form
tumors formation (teratomas) High ethical
controversy Less moral controversy
Uncertain legal status Less legal
controversy
23
the Scientific Foundations of Cardiac Repair
Stefanie Dimmeler, Andreas M. Zeiher, Michael
D. Schneider. The Journal of Clinical
Investigation Vol 115 Number 3 March 2005
Review Recent experimental studies and
early-phase clinical trials lend credence to
the visionary goal of enhancing cardiac
repair as an achievable therapeutic target.
24
Cell Types Peripheral blood- derived progenitor
cells, bone marrow, skeletal muscle myoblasts,
fat tissue derived multipotent stem cells and
embryonic stem cells.
25
Route of Application
26
Clinical Trials Intracoronary Progenitor Cells
for Acute Myocardial Infarction
Study
N
Cell
Cell No.
Safety
Myocardial
function
(106 )
type
Regional contractility endsystolic
volume perfusion
Strauer et al.
10
BMCs
28

Global contractility end systolic
volume viability
CPCs

16
59
TOPCARE-AMI
BMCs
213
similar results for both cell types
BMCs

30
2,460
BOOST
Global contractility
Fernandez-Aviles et al
Global contractility end systolic volume
20
BMCs
78

27
Potential Roles of Bone Marrow-Derived Cells in
Renal Protection/ Repair
Krause, D. et al. J. Clin. Invest.
20051151705-1708
28
Umbilical Cord Blood Cells and Brain Stroke
Injury Bringing in Fresh Blood to Address an
Old Problem.
Daniel A. Peterson Rosalind and Franklin
University of Medicine and Science, North
Chicago, USA
The Journal of Clinical Investigation Vol. 114
No.3 July 2004
Review evidence which suggests that delivery of
circulating CD34 human umbilical cord cells can
produce functional recovery in an animal stroke
model
29
Morphological Response of Stroke-Injured Brain to
Delivery of Umbilical Cord Blood Cells
Peterson, D. A. J. Clin. Invest. 2004114312-314
30
Stem cell transplant helps Brazilian walk again
A Brazilian woman who suffered a brain
haemorrhage that left her paralysed on one side
has regained her ability to walk and talk after
undergoing a stem cell transplant, hospital
officials say.
31
The patients lower limbs were paralyzed after an
accident in 1985 damaged her lower back and hips.
Afterward she spent her life in bed or in a
wheelchair The stem cell transplantation was
performed on Oct. 12, 2004 and in just three
weeks she started to walk with the help of a
walker. The team was co-headed by Chosun
University professor Song Chang-hun, Seoul
National University professor Kang Kyung-sun and
Han Hoon, Ph.D, from the Seoul Cord Blood Bank
(SCB).
32
Stem Cell Therapy for Skin Developed
By Kim Tae-gyu, Staff Reporter
A team of Korean scientists has developed a
breakthrough technology to heal skin damage, such
as burn injuries, by transplanting skin cells
enriched from stem cells.
The team, headed by Korea Institute of
Radiological and Medical Sciences researcher Son
Young-sook, revealed the medical technique of
using stem cells to mass produce skin cells. We
extracted skin stem cells from a burn patients
epidermis, cultured them and increased their
number by 200 times outside his body in two
weeks. Then we transplanted them back to the
patient and got a satisfactory result, the
47-year-old Son said.
33
Stem Cell Therapy for Skin Developed
34
Current Clinical Applications of Adult Stem Cells.
David A. Prentice http//www.lifeissues.org
Cancer Treatment Brain Tumors, Retinoblastoma,
Ovarian Cancer, Testicular Cancer, Breast
Cancer, Neuroblastoma
Anemias Sickle Cell Anemia, Congenital
Thrombocytopenia, Thalassemia, Congenital
Sideroblastic Anemia Autoimmune
Disease Stroke Immunodeficiency Cartilage and
Bone Disease Corneal Scarring Diseases of Central
Nervous System, Heart, Liver
35
U.S. President George W. Bush has endorsed
limited federal funding of embryonic stem cell
research. The complex and controversial issue has
divided members of his own party and pitted the
scientific community against religious leaders.
Bush said federal funds would only be used for
research on 60 existing embryo stem cell lines
"where a life-and-death decision has already been
made." The embryos for these lines have already
been destroyed
36
Americans Following the Issue of Stem Cell
Research
How closely have you been following the issue of
stem cell research?
Taking Our Pulse The PARADE/Research!America
Health Poll Charlton Research Company, 2005
37
Americans Favor Embryonic Stem Cell Research
(ESCR)
Do you favor or oppose medical research using
embryonic stem cells?
58
29
Taking Our Pulse The PARADE/Research!America
Health Poll Charlton Research Company, 2005
38
ESCR Policy Should Be Nationally Uniform
Do you believe there should be a uniform national
policy for medical research using embryonic stem
cells, or not?
Taking Our Pulse The PARADE/Research!America
Health Poll Charlton Research Company, 2005
39
Majority of Americans Favor Federal Funding for
ESCR
Do you favor or oppose federal funding for
medical research using embryonic stem cells?
Taking Our Pulse The PARADE/Research!America
Health Poll Charlton Research Company, 2005
40
Americans Favor Expanding U.S. Policy on ESCR
Although the initial discoveries were made by
scientists in the U.S., government-supported
scientists in China, South Korea, Singapore,
Great Britain and Israel are taking the lead in
medical research using embryonic stem cells.
Knowing this, do you favor or oppose expanding
the U.S. policy to permit more embryonic research?
Taking Our Pulse The PARADE/Research!America
Health Poll Charlton Research Company, 2005
41
Americans Favor Research Using Donated Eggs from
Fertility Clinics
Scientists can extract embryonic stem cells from
fertilized eggs that are voluntarily donated by
fertility clinic patients. These fertilized eggs
would otherwise be discarded. Knowing this, do
you favor or oppose embryonic research?
Taking Our Pulse The PARADE/Research!America
Health Poll Charlton Research Company, 2005
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