Group Four Project:
Embryonic Stem Cells
Source: http://www.nectareal.com
Embryonic Stem Cells:
Background
Retrieved from inner mass of an early-stage
embryo
4-5 days following fertilization by sperm
Consists of 50-150 cells
Isolating the the inner cell mass results in the
death of the human embryo
Embryonic stem cells are mainly valuable
because they are:
Pluripotent (ability to differentiate to become any
type of cell)
Able to replicate indefinitely to any kind of the
over 220 type of cell in the adult human body
Embryonic Stem Cells: History
In 1981, embryonic stem cells were independently
derived from embryos
Martin Evans and Matthew Kaufman of the University of
Cambridge pioneered a new technique for culturing mouse
embryos in the uterus to allow for an increase in cell
number, allowing for the derivation of embryonic cells from
these embryos
In 1981 Gail Martin, of the University of California,
San Francisco, published a paper in December and
coined the term “Embryonic Stem Cell”
In 1998, a breakthrough occurred when
James Thomson and his group of
researchers at the University of Wisconsin-
Madison, developed a technique to isolate
and cultivate human embryonic stem cells in
cell culture
Social Concerns
It’s more of an ethical issue as it has to do
with one’s morality.
Some believe embryonic stem cells for
research is an activity involves deliberate
attempt to destroy human life.
Embryonic stem cells can cause cancer when
and if they become malignant.
Economic Concerns
Many Clinics in the US have been set up to collect cells from the
people
The cells are stored to be used in the future
they can be used to cure health problems like organ transplant,
spinal cord injuries, birth defects, etc.
To run these clinics, millions and millions of dollars are used.
This money is mainly funded by the government.
But the thing is researchers are not even sure if this will ever be
possible
Now the question is: Is the money worth being spent for this?
Even if we are able to find a cure
Clinical Trials
Although embryonic stem cell research has not
progressed to the stages of completed clinical
research, the FDA have recently approved of a
couple of clinical trials on human embryonic
stem cells. The successes of these trials are
not certain, but the hopes are high. At this
stage, the main priority is to make sure the
patients are kept safe. As well, there are a
couple of preclinical trials that have been
completed with mostly good, but the occasional
varying result
Geron: The Hope
To use oligodendrocyte progenitor cells
(GRNOPC1),
derived from
human embryonic
stem cells (hESC),
to help people
that have suffered
from spinal cord injuries by injecting the cells
directly into the spinal cord lesion
Geron: The Plan
Patients in the trial cannot have been
injured for more than 14 days prior to
receiving GRNOPC1
Patients will be AIS (the ASIA
Impairment Scale ) – Grade A (most severe
loss of locomotor and sensory activity)
thoracic spinal cord injuries
Patients will be monitored for 15 years after
the injection
The trial is to be conducted at seven different
medical centres in the U.S.
Geron: Preclinical Trial
Animals both suffering from spinal cord injuries
and uninjured were monitored for 12 months
after receiving and injection of GRNOPC1 to see
if teratomas (a type of germ cell tumor, can be
benign or malignant) formed.
Animals injected with clinical grade GRNOPC1 did not
form any teratomas
Rats and mice with spinal cord injuries were
given GRNOPC1, acute and chronic toxicology
studies were performed, as well as multiple
hematology, clinical chemistry, urinalysis, and
gross and microscopic pathology tests
No significant toxicity were found
GRNOPC1 was not found outside of central nervous
system
Geron: Preclinical Trials
Rats with spinal cord injuries were
administered with GRNOPC1 and checked
for allodynia (Pain from things that are not
usually painful
No allodynia was found
in vitro studies were used to test if the
allograft will be rejected (Direct Allogeneic
Immune Response to GRNOPC1)
No Direct Allogeneic Immune Response were
found
Cysts were found
Geron: Problems
As stated before, animals studies have
shown GRNOPC1 to be ineffective if used
more than three months after the injury.
Cysts might form as a result of the injection
ACT: MA09-hRPE
A type of drug derived from embryonic stem
cells in hopes of treating Stargardt’s Macular
Dystrophy, a type of blindness
Approved earlier this year, there is not much
more information available about this
particular clinical trial
Although, ACT has in place the Blastomere
Program, a way to generate hESC without
killing the embryo
International Consequences:
Geron
If this trial succeeds, then people around the
world with spinal injuries that are unable to
walk could have the opportunity again
However, as many nations are opposed to
stem cell research, especially embryonic
stem cell research, people in those nation
may lose out the chance, creating more
tension between nations.
International Consequences:
ACT
If the drug works, there could be new hope
for all the blind people in the world. The
treatment for Stargardt’s Macular Dystrophy
can lead to breakthroughs for other kinds of
blindness
If the Blastomere Program works, then there
will be one less objection for using embryonic
stem cells for medical advancements.
Embryonic Stem Cells: clinical
uses
It is mainly argued that because the embryonic stem cells can only be
obtained from a human embryo, it is morally wrong to treat diseases.
Due to this arguable factor, countries like Canada and America aren’t
studying in depth about this particular type of stem cell.
Embryonic stem cells are “pluripotent”, meaning they are capable of
forming embryonic tissue.
Researchers extract stem cells from 5-7 day old blastocyst.
Stem cells can divide in culture to form more of their own kind,
thereby creating a stem cell line.
These cells help generate healthy tissues needed by patients.
More than 100 human embryonic stem cell lines have been derived
worldwide.
Only 22 of these lines are eligible for federal funding in the USA.
Stem cells can be used to generate healthy and functioning
specialized cells, which can then replace diseased or dysfunctional
cells.
Embryonic Stem Cells: clinical
uses (continued)
It’s similar to the process of organ transplantation, only this
treatment consists of transplanting cells rather than organs.
Bone marrow transplants is an example of cell therapy, were
the stem cells in the donor’s marrow is used to replace the
blood cells of the victims of leukemia.
Cell therapy is also being used in experiments to graft new skin
cells to treat serious burn victims, and grow new corneas for
the sight impaired.
The goal is for healthy cells to become integrated in the body
and start functioning like the patient’s own cells.
Any diseases in which there is tissue degeneration can be a
potential candidate for stem cell therapies.
Applications of stem cells
Cell replacement therapy could treat injuries
and various genetic and degenerative
conditions, including muscular dystrophies,
retinal degeneration, Alzheimer’s disease,
Parkinson’s disease, Heart disease, Severe
burns, arthritis, diabetes, spinal chord
injuries, and blood disorders such as
haemophilia.
Advantages of Embryonic
Stem Cell Usage
They have the potential to make any body
cell.
One cell line may be able to potentially
supply endless amounts of cells.
Human embryos can be obtained from
fertility clinics, and are thereby easily
available to us.
Disadvantages of Embryonic
Stem Cell Use
Inducing the cell type needed to treat a specific disease must
be defined and optimized, and this is thereby difficult to control.
It is possible that transplanted cells would differ in their immune
profile from that of the recipient and therefore would be
rejected.
It’s also ethically controversial for those who believe life begins
at conception.
improper regulation of genes can lead to uncontrolled cell
division and tumor formation. This is a special concern with
cells that have been cultured in the laboratory for a period of
time, because they may regulate their genes differently than
they would in the body.
Future Use of Embryonic Stem
Cells
The production of cardiac muscle cells, which have thus far
been evasive, would hold tremendous promise for the number
one killer: heart disease.
Researchers could study the beneficial and toxic effects of new
medication pluripotent stem cells that have been developed to
mimic disease processes.
Through more in-depth studies of pluripotent stem cells, it can
lead to the identifying factors responsible for differentiation of
stem cells into specialized cell types.
Future therapies will rely on our ability to manipulate stem cells
in a way that can be accepted by the human body as normal.
Human Embryonic Stem Cell Research offers
great promise of cures for otherwise incurable
conditions such as spinal cord injuries,
Alzheimer’s, Parkinson’s, etc.
Research is aimed to find the appropriate source
of stem cells for a given indication (of disorders).
Ways of expanding and perpetuating these cells in
culture.
The best route of administrating these cells.
Also, various methods to overcome rejection.
Potential Clinical Uses
Human embryonic stem cells could be used to test new drugs.
new medications could be tested for safety on differentiated cells
generated from human embryonic stem cell lines
differentiated cells are less specialized cells that undergo a process
becoming a more specialized cell type
Cancer cell lines used to screen potential anti-tumor drugs, with
embryonic stem cells, drug testing could be done in a larger
range of cell types
Generation of cells and tissues could be used for cell-based
therapies.
Treating diseases for which there are no known cures.
Stem cells, directed to differentiate into specific cell types, could
offer a renewable source of replacement cells and tissues to treat
diseases
ex.Alzheimer's diseases, spinal cord injury, heart disease
Human embryonic stem cells have potential to form insulin-
producing cells that can be transplanted into diabetic patients,
curing diabetes
Stem cell therapy could regenerate muscle and bones damaged by
injury or genetic disease
May become possible to generate healthy heart muscle cells in
laboratory and then transplant those cells into patients with
chronic heart disease.
Cells could repair by secreting growth factors around tissues
Possible to direct the differentiation of embryonic stem cells or
adult bone marrow cells into heart muscle cells
Stem cells could stimulate the growth of human tissues assisting
in healing wounds quicker
Possible method for tissue regeneration: place adult stem cell
inside a tissue bed in a wound bed and allow stem cells to
stimulate differentiation in the tissue bed cells
Could potentially treat Azoospermia
Male does not have measurable level of sperm in his semen
causing infertility
Sources
http://www.advancedcell.com/our-technology/research-programs/blastomere-program/
http://www.geron.com/media/pressview.aspx?id=1235
http://www.geron.com/GRNOPC1Trial/grnopc1-sec2.html
http://www.geron.com/GRNOPC1Trial/grnopc1-sec3.html
http://www.geron.com/GRNOPC1Trial/grnopc1-sec4.html
http://singularityhub.com/2010/03/02/act-gains-fda-approval-for-embryonic-stem-cell-derived-therapy/
http://machineslikeus.com/news/cautionary-warning-future-stem-cell-applications
http://www.actionbioscience.org/biotech/pecorino2.html
http://www.slideshare.net/doctorrao/stem-cells-and-clinical-applications-1710672
http://stemcells.nih.gov/info/basics/basics6.asp
http://www.reproduction-online.org/cgi/content/full/128/3/259
http://www.aaas.org/spp/sfrl/projects/stem/report.pdf
http://elibrary.bigchalk.com
http://www.buzzle.com/articles/embryonic-stem-cell-research-pros-and-cons.html
http://www.suite101.com/content/pros-and-cons-of-stem-cell-research--ethical-issues-a254568
http://www.leaderu.com/science/promisestemcell.html