ADULT VS. EMBRYONIC STEM CELL RESEARCH
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1) Human embryonic stem cell lines have proven difficult to
develop and maintain.
1 "The scientists [from South Korea that created the
first human clone embryo] used 242 eggs from 16 women donors. Because
they started with a huge number of eggs, they could vary the methods
they used and the media in which they grew the cells. They derived 30
blastocysts and from these tried 20 times to produce a line of embryo
stem cells. The success rate was not high, possibly because of
chromosomal abnormalities that appeared in the reprogramming or possibly
because of subtle variations in the techniques they used. They ended up
with just one line of stem cells, cultivated from a blastocyst that had
been cloned from nuclear material taken from cumulus cells belonging to
the woman who had donated the egg in the first place." Radford, Tim.
"Korean scientists clone 30 human embryos." British Medical
Journal 328 (2004). Original article: Hwang, Woo Suk, et al.
"Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a
Cloned Blastocyst," Science 303 (2004): 1669-1674.
2 "Chromosomal abnormalities are commonplace in human
embryonal carcinoma cell lines and in mouse embryonic stem-cell lines
and have recently been reported in human embryonic stem-cell
lines.” C. Cowan et al., “Derivation of Embryonic Stem-Cell
Lines from Human Blastocysts,” New England Journal of
Medicine 350 (2004): 1353-1356.
3 "The approved [human embryonic stem] cells have all been
cultured in the presence of mouse cells--called 'feeder cells'--that
apparently supply needed growth factors. It is believed that
contamination from mouse viruses or proteins may make such cells
unsuitable for introduction into humans for therapeutic purposes."
Kennedy, Donald. "Stem Cells: Still Here, Still Waiting."
Science 300 (2003): 865.
4 "The Jones Institute for Reproductive Medicine, located
in Norfolk, Virginia, announced in July 2001 that it had created human
embryos via IVF for the purpose of deriving human embryonic stem cells.
A total of 162 oocytes (eggs) from 12 women were collected and
fertilized with sperm donated by two men; 110 fertilized eggs developed,
of which 40 developed to the blastocyst stage. The inner cell masses
were removed from the blastocysts resulting in three healthy embryonic
stem cell lines." Johnson, Judith A. "Report for Congress: Stem Cell
Research." Congressional Research Service, July 26, 2004. Accessed at http://www.cnie.org/nle/crsreports/RL31015.pdf
on July 21, 2004.
2) Pure embryonic stem cell cultures are difficult to
5 "Scientists are still working on developing proper
conditions to differentiate embryonic stem cells into specialized cells.
As embryonic stem cells grow very fast, scientists must be very careful
in fully differentiating them into specialized cells. Otherwise, any
remaining embryonic stem cells can grow uncontrolled and form tumors."
"Frequently Asked Questions." International Society for Stem Cell
6 "[W]ithin the [embryonic stem cell] research community,
realism has overtaken early euphoria as scientists realize the
difficulty of harnessing ESCs safely and effectively for clinical
applications. After earlier papers in 2000 and 2001 identified some
possibilities, research continued to highlight the tasks that lie ahead
in steering cell differentiation and avoiding side effects, such as
immune rejection and tumorigenesis.” Hunter, Philip.
“Differentiating Hope from Embryonic Stem Cells.” The
Scientist 17 (2003): 31. Accessed on July 23, 2004 at www.the-scientist.com/yr2003/dec/hot_031215.html.
3) Embryonic stem cells are unstable and mutate in
7 "Within the laboratory from a very few cells you
could grow a roomful of [embryonic] cells very easily. But there is an
issue we don't know much about, and that is obviously there is a finite
probability that at every cell division that a genetic mutation will
appear… mutations do occur in these cells, and they are of the
nature of making these cells susceptible to formation of tumors."
Gearhart, John. "Medical Promise of Embryonic Stem Cell Research
(Present and Projected)". President's Council on Bioethics, April 25,
8 "It is not yet known whether any preparation of human ES
cells (generally believed to be much longer-lived than adult stem cells)
will continue to grow 'indefinitely,' without undergoing genetic
changes." "Recent Developments in Stem Cell Research." Monitoring Stem
Cell Research. The President's Council on Bioethics, January 2004.
4) Differentiation protocols for many cell types have not
9 This is most likely due to what the National
Institutes of Health describes as the "lack of a universally accepted
standard for determining what characteristics will predict the ability
of such cells to be…differentiated or…useful for the
development of therapies." The NIH Update from August 27, 2001 states,
"…It is noteworthy that there have been no reported comparative
studies on the characteristics of human embryonic stem cells from
different derivations." "NIH Update on Embryonic Stem Cell Lines."
August 27, 2001.
Accessed July 6, 2004 at: (http://diabetes.about.com/library/blnews/blnstemcellupdateNIH801.htm).
5) Cell types that have been differentiated often act
10 University of Calgary scientists reported that
the insulin-producing cells derived from embryonic stem cells are not
the "beta cells" needed to reverse diabetes. They failed to function as
normal beta cells and to produce the insulin when it was needed. When
placed in mice, they did not reverse diabetes but only formed tumors. S.
Sipione et al., "Insulin expressing cells from differentiated embryonic
stem cells are not beta cells." Diabetologia 47 (2004):
11 “Rarely have specific growth factors or culture
conditions led to establishment of cultures containing a single cell
type…. [T]he possibility arises that transplantation of
differentiated human ES cell derivatives into human recipients may
result in the formation of ES cell-derived tumors… Irrespective of
the persistence of stem cells, the possibility for malignant
transformation of the derivatives will also need to be addressed.”
Odorico, J.S. et al, “Multilineage differentiation from human
embryonic stem cell lines.” Stem Cells 19 (2001):
12 “Long-term culture of mouse ES [embryonic stem]
cells can lead to a decrease in pluripotency and the gain of distinct
chromosomal abnormalities. Here we show that similar chromosomal
changes, which resemble those observed in hEC [human embryonal
carcinoma] cells from testicular cancer, can occur in hES [human
embryonic stem] cells…. The occurrence and potential detrimental
effects of such karyotopic changes will need to be considered in the
development of hES cell-based transplantation therapies.” Draper,
J. et al., “Recurrent gain of chromosomes 17q and 12 in cultured
human embryonic stem cells.” Nature Biotechnology 22
6) When embryonic-derived cells have been placed in animals,
cancerous tumors have formed.
13 “There are still many hurdles to clear
before embryonic stem cells can be used therapeutically. For example,
because undifferentiated embryonic stem cells can form tumors after
transplantation in histocompatible animals, it is important to determine
an appropriate state of differentiation before transplantation.
Differentiation protocols for many cell types have yet to be
established. Targeting the differentiated cells to the appropriate organ
and the appropriate part of the organ is also a challenge.” E.
Phimister and J. Drazen. “Two Fillips for Human Embryonic Stem
Cells.” New England Journal of Medicine 350 (2004):
14 Harvard scientists reported in the Proceedings of the
National Academy of Sciences that they injected embryonic stem cells
into 19 mice with Parkinson's disease. Five out of the 19 mice developed
tumors and died. Bjorklund, L. M., R. Sanchez-Pernaute, et al.
"Embryonic stem cells develop into functional dopaminergic neurons after
transplantation in a Parkinson rat model." Proceedings of the
National Academy of Sciences 99 (2002): 2344-2349.
7) To address the problem of immune rejection, researchers
have proposed cloning individual patients to obtain compatible embryonic
15 “ES [embryonic stem] cells and their
derivatives carry the same likelihood of immune rejection as a
transplanted organ because, like all cells, they carry the surface
proteins, or antigens, by which the immune system recognizes invaders.
Hundreds of combinations of different types of antigens are possible,
meaning that hundreds of thousands of ES cell lines might be needed to
establish a bank of cells with immune matches for most potential
patients. Creating that many lines could require millions of discarded
embryos from IVF clinics… At present, the only sure way to
circumvent the problem of immune rejection would be to create an ES cell
line using a patient's own genetic material through nuclear transfer or
cloning.” R. Lanza and N. Rosenthal. “The Stem Cell
Challenge.” Scientific American June (2004): 93-99.
16 "If [embryonic stem cell] research is to prove
successful, many hurdles will have to be surmounted. Scientists will
have to learn how to culture stem cells reliably in the laboratory and
steer them toward development of the desired tissue types. It will have
to be shown that these cells can be safely transplanted into the human
body. Even if this is successful, major problems of immunological
incompatibility and tissue rejection will remain…Therapeutic
cloning promises an 'end run' around all these problems. R. Lanza et al,
"The Ethical Validity of Using Nuclear Transfer in Human
Transplantation." Journal of the American Medical Association
17 "Human cloning could yield numerous identical embryos,
could provide for the study of stem cells derived from individuals known
to possess genetic diseases, and might eventually yield transplantable
tissues for regenerative medicine that would escape immune rejection."
"The Meaning of Human Cloning: An Overview." Human Cloning and Human
Dignity: An Ethical Inquiry. President's Council on Bioethics, July
8) Besides the ethical inadmissibility of human cloning, some
researchers have questioned whether cloning will truly solve the
Cells taken from cloned human beings are not normal. Women's groups
and others have rightly condemned the commercialization of women
required to gain the millions of human eggs needed for such cloning.
18 "In order to conduct so-called 'therapeutic' cloning on
the scale that would yield just a portion of the benefit cloning
advocates promise, one would need to harvest a vast number of human eggs
from women of child bearing age…The ‘egg dearth' is a
mathematic certainty. It is one reason why some researchers say that
therapeutic cloning will not be a generally available medical
treatment…Recently biotech researchers Jon S. Odorico, Dan S.
Kaufman, and James A. Thompson admitted the following in the research
journal Stem Cells: ‘The poor availability of human oocytes
(eggs), the low efficiency of the nuclear cell procedure, and the long
population-doubling time of human ES cells make it difficult to envision
this [therapeutic cloning to obtain stem cells] becoming a routine
clinical procedure even if ethical considerations were not a significant
point of contention.'" Sam Brownback, "Cloning: A Risk to Women?" Senate
Commerce Subcommittee on Science, Technology and Space, March
19 "With therapeutic cloning, scientists would make an
embryo clone of the patient, remove its stem cells and use them to grow
needed tissue, which presumably would not be rejected…The Jones
Institute for Reproductive Medicine in Norfolk, Va., using in vitro
fertilization rather than cloning, started with 162 women's eggs and got
three stem cell lines. Advanced Cell Technology, in the first cloning of
human embryos, started with 71 eggs and got no stem cells because no
embryos developed into proper blastocysts." Pollack, Andrew. “Use
of Cloning to Tailor Treatment Has Big Hurdles, Including Cost.”
The New York Times, December 18, 2001. http://www.genetics-and-society.org/resources/items/20011218_nytimes_pollack.html
9) Even if each of these problems were somehow solved, at a
cost of over $200,000 per patient, only the very wealthy could afford
20 "This analysis of the limited body of literature raises
concerns about the feasibility and relevance of therapeutic cloning, in
its current embodiment, for human clinical practice. A crucial
difference is that, although 100 mouse oocytes can be obtained from a
few superovulated females at a cost of [approximately] $20, human
oocytes must be harvested from superovulated volunteers, who are
reimbursed for their participation. Add to this the complexity of the
clinical procedure, and the cost of a human oocyte is [approximately]
$1,000-2,000 in the U.S. Thus, to generate a set of customized ntES
(nuclear transfer embryonic stem) cell lines for an individual, the
budget for the human oocyte material alone would be [approximately]
$100,000-200,000. This is a prohibitively high sum that will impede the
widespread application of this technology in its present form."
Mombaerts P. "Therapeutic cloning in the mouse." Proceedings of the
National Academy of Science 100 (2003):11924-5.
21 "Many scientists now acknowledge that even if
"therapeutic cloning" can be perfected--a huge 'if,' despite the South
Korean success--it would probably be too impractical and expensive to
ever become widely available...Indeed, the potentially high cost of, and
intense controversy over, therapeutic cloning have made venture
capitalists reluctant to invest in human cloning biotech." Smith,
Wesley, J. "On My Mind: Watch out. You may soon be paying for cloning
research that the private sector won't." Forbes, March 2,
1) “Adult” (non-embryonic) stem cells have been
found in cord blood, placenta, bone marrow, fat, teeth and other
22 "One extremely interesting finding of the past few years
has been the discovery of neuronal stem cells, indicating that cell
replenishment was possible within the brain (something previously
considered impossible.) Neuronal stem cells have been isolated from
various regions of the brain including the more-accessible olfactory
bulb as well as the spinal cord, and can even be recovered from cadavers
soon after death. Evidence now exists that neuronal stem cells can
produce not only neuronal cells but also other tissues, including blood
and muscle." Prentice, David. "Adult Stem Cells." Monitoring Stem Cell
Research, Appendix K; President's Council on Bioethics. January
23 "These results indicate that adult skeletal muscle
contains a rich source of hematopoietic progenitors for both myeloid and
lymphoid lineages... these data document that satellite cells and
muscle-derived stem cells represent distinct populations and demonstrate
that muscle-derived stem cells have the potential to give rise to
myogenic cells via a myocyte-mediated inductive interaction." Asakura A
et al., “Myogenic specification of side population cells in
skeletal muscle.” Journal of Cell Biology 159 (2002):
24 "In this study, we characterized the self-renewal
capability, multi-lineage differentiation capacity, and clonogenic
efficiency of human dental pulp stem cells (DPSCs). DPSCs were capable
of forming ectopic dentin and associated pulp tissue in vivo.
Stromal-like cells were reestablished in culture from primary DPSC
transplants and re-transplanted into immunocompromised mice to generate
a dentin-pulp-like tissue, demonstrating their self-renewal
capability…These results demonstrate that human dental pulp stem
cells possess stem-cell-like qualities, including self-renewal
capability and multi-lineage differentiation." Gronthos S et al., "Stem
cell properties of human dental pulp stem cells." Journal of Dental
Research 81 (2002): 531-535.
25 "In this study, we determined if a population of stem
cells could be isolated from human adipose tissue. Human adipose tissue,
obtained by suction-assisted lipectomy (i.e., liposuction), was
processed to obtain a fibroblast-like population of cells or a processed
lipoaspirate (PLA). In conclusion, the data support the hypothesis that
a human lipoaspirate contains multipotent cells and may represent an
alternative stem cell source to bone marrow-derived MSCs." Zuk PA et al,
“Multilineage cells from human adipose tissue: implications for
cell-based therapies.” Tissue Engineering 7 (2001):
26 "We investigated the potential use of rat amniotic
epithelial (RAE) cells as donor cells for transplantation-based therapy
in brain ischemia. These results suggest that intracerebral
transplantation of amniotic epithelial cells may have therapeutic
potential for the treatment of ischemic damage in neuronal disorders."
Okawa H et al., “Amniotic epithelial cells transform into
neuron-like cells in the ischemic brain.” NeuroReport 12
27 "We describe here the isolation of stem cells from
juvenile and adult rodent skin. Because these cells (termed SKPs for
skin-derived precursors) generate both neural and mesodermal progeny, we
propose that they represent a novel multipotent adult stem cell and
suggest that skin may provide an accessible, autologous source of stem
cells for transplantation." Toma JG et al, “Isolation of
multipotent adult stem cells from the dermis of mammalian skin.”
Nature Cell Biology 3 (2002): 778-784.
2) Adult stem cells found in one type of tissue can repair damage in
another tissue type. Multipotent adult progenitor cells (MAPC) found in
bone marrow can develop into all of the 210 different types of tissue in
the human body.
28 "MAPC appear to have pluripotent potential both in vitro
and in vivo. Furthermore, they appear to proliferate without obvious
senescence when maintained under very stringently controlled culture
conditions. Because of these reasons, some have argued that they might
be a viable alternative to ES cells." Verfaillie, Catherine.
"Multipotent Adult Progenitor Cells: An Update." Monitoring Stem Cell
Research, President's Council on Bioethics. January 2004; Appendix J.
Accessed July 6, 2004 at http://www.bioethics.gov/reports/stemcell/appendix_j.html
29 "Analysis of serial contrast-enhanced MRI suggests that
intracoronary infusion of adult progenitor cells in patients with AMI
beneficially affects postinfarction remodeling processes. The migratory
capacity of the infused cells is a major determinant of infarct
remodeling, disclosing a causal effect of progenitor cell therapy on
regeneration enhancement. These data indicate that cell therapy may
beneficially modify the healing process of myocardial infarction."
Britten MB et al., "Infarct remodeling after intracoronary progenitor
cell treatment in patients with acute myocardial infarction."
Circulation 108 (2003): 2212-2218.
3) Adult stem cells can be harvested from each patient, multiplied in
culture and transplanted back into the patient. They genetically match
and therefore are not subject to immune rejection.
30 "Researchers in the U.S. and Taiwan used corneal adult
stem cells to grow new corneas for patients with previously untreatable
eye damage. Adult stem cells were taken from the patients themselves in
16 cases, or a family member for 4 other patients. The cells were then
grown in culture before transplantation onto the damaged eyes. Sixteen
of the 20 patients had improved vision." Schwab IR et al.
“Successful transplantation of bioengineered tissue replacements
in patients with ocular surface disease.” Cornea 19
31 R. Galli, et al. transformed neural stem cells into
muscle cells, not only in culture, but after injection into mice.
“With adult stem cells there would also be the possibility of
auto-transplantation, eliminating all the problems of immunological
compatibility and rejection.” Transplant rejection would be a
significant problem if using embryonic stem cells. Galli, R. et al.
“Skeletal myogenic potential of human and mouse neural stem
cells.” Nature Neuroscience 3 (2000): 986-991.
4) Adult stem cells work in multiple ways to repair damaged
tissue. They fuse with cells in damaged organs and initiate
repair. They take cues from tissue that has been damaged and begin to
directly produce cells. Sometimes they secrete substances that cause
undamaged cells to divide and replace damaged or dead cells.
32 "Because hematopoietic (blood forming) stem cells (HSCs)
can restore and maintain blood formation following transplantation into
immune deficient hosts, growth of HSCs in culture is important for many
clinical applications…These adult stem cells efficiently rescued
immune-compromised mice and generated all blood cells." Ó. P. do
Pinto, et al. “Hematopoietic Progenitor/Stem Cells Immortalized by
Lhx2 Generate Functional Hematopoietic Cells in vivo." Blood (2002):
33 A team of researchers in Tampa, Florida reported that
"cord blood stem cells are beneficial in reversing the behavioral
effects of spinal cord injury, even when infused 5 days after injury."
Garbuzova-Davis, Svitlana, et al. "Intravenous Administration of Human
Umbilical Cord Blood Cells in a Mouse Model of Amyotrophic Lateral
Sclerosis: Distribution, Migration, and Differentiation." Journal of
Hematotherapy and Stem Cell Research 12 (2003): 255–270.
34 "[Adult stem cells] appear to be able to respond at
least in some respects to cues that are present in certain organs to
differentiate into the cell type that is specific for that
organ…You can take a single [adult stem] cell, and give it to a
mouse that was lethally irradiated so it has no blood, and this cell can
recreate the red cells, the white cells, platelets, lymphocytes, for the
lifetime of that animal…It has been shown for bone marrow
cells…that if you transplant these into an animal that was
irradiated, and you look in tissues outside of the blood, that you can
actually find, for instance, skeletal-muscle cells, heart muscle cells,
or endothelial cells, that are now derived from this donor hematopoietic
cell." Verfaillie, Catherine. "Medical Promise of Adult Stem Cell
Research (Present and Projected)." President's Council on Bioethics,
April 25, 2002.
5) Since adult stem cells require limited, if any,
manipulation, and are readily available from a number of sources, the
cost for their clinical application will be far more reasonable than any
application from embryonic stem cells.
6) There are no ethical concerns in their use, making them
acceptable to virtually all patients and healthcare providers and a
bipartisan point of agreement for federal funding.
7) Adult stem cells are already providing cures in animals
and clinical human trials.
35 Science News reported in April of 2001 that stem cells
were transplanted into the spinal cords of rats after nine days of
paralysis. They were able to stand and walk, though not perfectly,
within two weeks. Seppa, N. “Stem cells repair rat spinal cord
damage.” Science News, April 12, 2001.
36 David Prentice, PhD, wrote in "Adult Stem Cells" that
many groups have used bone marrow derived stem cells in treatment of
patients with damaged cardiac tissue. "Results from these clinical
trials indicate that bone marrow derived stem cells, including cells
from the patients themselves, can regenerate damaged cardiac tissue and
improve cardiac performance in humans," Dr. Prentice said. Prentice,
David. "Adult Stem Cells." Do No Harm, July 2003. Accessed July 6, 2004
37 The Lancet reported that patients' bone marrow improved
blood circulation in gangrenous limbs so well that amputation was
avoided. Tateishi-Yuyama E et al.; “Therapeutic angiogenesis for
patients with limb ischaemia by autologous transplantation of
bone-marrow cells: a pilot study and a randomised controlled
trial.” Lancet 360 (2002): 427-435.
38 "Here we present the results of the first human
autologous transplantation of neural stem cells and stem cell-derived
dopaminergic neurons. These results strongly suggest that autologous
transplantation of neural stem cell-derived dopamine-producing cells may
be an effective restorative therapy for Parkinson's Disease. At one year
post-transplantation, total clinical scores improved by 83%. Motor
scores improved by 88%." Levesque, M and Neuman, T. "Autologous
transplantation of adult human neural stem cells and differentiated
dopaminergic neurons for Parkinson's disease: one-year post-operative
clinical and functional metabolic results." American Association of
Neurological Surgeons, April 2002. http://www.aans.org/Library/Article.aspx?ArticleId=12096