Stem Cell Research

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Stem Cell Research Human Cloning
Raising the Questions Scientific Research
William S. Oetting, Ph.D. Department of Medicine
- Genetics Institute of Human Genetics Universit
y of Minnesota
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Sources of Stem Cells
Embryonic Stem Cells Inner Cell Mass Adult St
em Cells Normally in adult tissue Adult Deriv
ed Embryonic Stem Cells Inner Cell Mass Embry
onic Germ Cells Germinal ridge of a 5-10 week fe
tus
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4 days
http//www.worldnetdaily.com/images/stemcell1.gif
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Stem cell definition
Stem cell differentiates
Stem cell self-replicates
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Stem cells have two important characteristics
that distinguish them from other types of cells.
First, they are unspecialized cells that renew
themselves for long periods through cell
division. Stem cells do not age.
The second is that under certain physiologic or
experimental conditions, they can be induced to
become cells with special functions such as the
beating cells of the heart muscle or the
insulin-producing cells of the pancreas.
http//stemcells.nih.gov/infoCenter/stemCellBasics
.asp
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Different Types of Stem Cells
Totipotent stem cells can give rise to all the
different types of cells in the body. A
fertilized egg is considered totipotent.
Pluripotent stem cells can give rise to any type
of cell in the body except those needed to
develop a fetus. Multipotent stem cells can gi
ve rise to multiple different cell types.
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Different Types of Stem Cells
http//www.worldnetdaily.com/images/stemcell2.gif
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How are human embryonic stem cells lines created?
Embryonic stem cells are derived from embryos
that develop from eggs that have been fertilized
in vitro. The embryos from which human embryoni
c stem cells are derived are typically four or
five days old and are a hollow microscopic ball
of cells called the blastocyst.
The inner cell mass is removed and the cells dis
sociated into single cells. The cells are then
plated on irradiated mouse cells.
The cells are then subcloned to maintain the cel
l line.
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http//www.erin.utoronto.ca/w3bio380/Lectsked/Lec
t12/Cleavage.htma12
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The developing fetus itself is the area marked as
"ICM" (inner cell mass) The blastocoel cavity in
the center is marked as "C The trophectoderm c
ells that will form the placenta surround the
cavity - one is marked with a "T"
http//www.advancedfertility.com/blastocystimages.
htm
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Odorico et al., Stem Cells 19193, 2001
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Mouse fibroblast feeder cells
ES cell colony
University of Wisconsin
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http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/B/Blood.html
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Hematopoietic colony-forming cells derived from
human embryonic stem cells Dan S. Kaufman, et a
l., PNAS, 9810716-10721, 2001
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Human ES cell differentiates into multiple
tissues in a culture dish
BLOOD CELLS
KAUFMAN DS PNAS 9810716, 2001
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Excitement surrounding ES cells

• Do not age
• Are pluripotent
• May be used to treat many (all?) diseases?
• Used to understand development
• Testing of new drugs

Controversy surrounding ES cells

• Allogeneic (from donor, not patient him/her self)
  
  
• Teratomas (benign tumors)
• Destruction of the blastocyst

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Adult Stem Cells
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http//stemcells.nih.gov/infoCenter/stemCellBasics
.asp
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Adult Stem Cells
Adult stem cells typically generate the cell
types of the tissue in which they reside.
A blood-forming adult stem cell in the bone marr
ow, for example, normally gives rise to the many
types of blood cells such as red blood cells,
white blood cells and platelets.
It was initially thought that a blood-forming ce
ll in the bone marrow which is called a
hematopoietic stem cell could only give rise to
hematopoietic cells. Recently it has been show
n that these cells can give rise to other tissues
such as neurons, liver cells that can be made to
produce insulin, and hematopoietic stem cells
that can develop into heart muscle.
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http//stemcells.nih.gov/infoCenter/stemCellBasics
.asp
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A number of organ specific stem cells have been
identified including hematopoietic, endothelial,
muscle, mesenchymal, neural, gastrointestinal,
hepatic, and epidermal stem cells. In contrast to
ES cells, adult stem cells are derived from adult
tissue. Hematopoietic stem cells have been used
for transplantation. Neural stem cells, prese
nt in fetal and adult brain, could be used for
treatment of Parkinson's disease, Huntington's
disease, Alzheimers disease, multiple sclerosis,
and spinal cord injury. Insulin producing isle
t cells to treat diabetes mellitus using the
patient's own islet stem cells, or using ex vivo
generated / expanded islet cells from allogeneic
donors. Endothelial stem cells in the blood and
marrow of humans and animals could be used to
induce neovascularization, or to prevent tumor
angiogenesis. Mesenchymal stem cells present in
bone marrow are capable of generating cartilage
and bone, are being tested for their ability to
restore bone and cartilage defects
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http//stemcells.nih.gov/infoCenter/stemCellBasics
.asp
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There are three main approaches to cell therapy
in regenerative medicine Allogeneic embryonic
stem cells. While these stem cells are
totipotent, they are not compatible with the
patients DNA, thereby having a high risk of
rejection by the patients immune system. The
word allogeneic literally means other DNA type.
The companies pursuing this strategy typically
intend to address this problem trough
administration of immunosuppressant drugs along
with the cell therapy.   Autologous adult stem c
ells. These are stem cells taken from the patient
and coaxed into replacement cells for the
patients degenerative disease. While the
resulting cells are of the patients own DNA, only
a limited number of cell types can be created
from these stem cells, thereby limiting the
usefulness of this approach. Autologous embryon
ic stem cells. ACTs strategy is to use stem
cells cloned directly from the patients own
cells, thereby generating totipotent stem cells
that are not rejected by the patient.
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Human therapeutic cloning. Robert P. Lanza et
al. Nature Medicine 5, 975 - 977 (1999)
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Images of the Somatic Cell Nuclear Transfer
Process
Enucleation
The recipient oocyte is held by a glass pipette
(left side of each frame), while a glass needle
is used to remove the genetic material in the
process of enucleation. Cell Transfer
A cell containing the genetic material from the
donor is placed inside the Zona Pellucida.  An
electrical pulse is then applied across the two
cells, causing their membranes to fuse into one
complete cell.
http//www.advancedcell.com/scnt.htm
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http//www.advancedcell.com/NBT-2002-img.htm
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Excitement surrounding adult derived ES cells

• Are pluripotent
• May be used to treat many (all?) diseases?
• They are autologous

Controversy surrounding adult derived ES cells

• A blastocyst is created
• Requires high technology to create them
• Several trials are necessary for a single success