|
In Guidelines issued 8/23/00 for
Research Using Human Pluripotent Stem Cells, the National Institutes of
Health (NIH) makes several misleading statements regarding the potential
of adult stem cells for scientific and medical advancement. The following
critique was first issued by Do No Harm on 8/28/00; it has been updated
(5/01) to reflect new research developments.
The NIH statements on adult stem cells remain unchanged. The facts then, and even more so now, undermine the NIH's rationale for funding destructive human
embryonic stem cell research:
NIH: "[S]tem cells for all
cell and tissue types have not yet been found in the adult human.
Significantly, cardiac stem cells or pancreatic islet stem cells have not
been identified in adult humans."
FACT:
Neither have cultured human embryonic stem cells been made to
differentiate into all tissue types, including cardiac or pancreatic stem
cells. However, adult stem cells for these tissues have
been identified in mice, and adult pancreatic stem cells have been
used to reverse diabetes in mice ("Reversal of insulin-dependent
diabetes using islets generated in vitro from pancreatic stem cells," Nature
Medicine 6, 278-282; March, 2000).
This advance with adult stem cells took place over a year before any report of making insulin-producing cells from mouse
embryonic stem cells; and the adult stem cells successfully reversed
diabetes in the mice, whereas mice receiving embryonic stem cells still
died from diabetes. As with
most biological discoveries, animal models have paved the way for clinical
uses in humans; we should expect that these same adult stem cells to be
present in humans.
Moreover, while human embryonic stem cells have yet
to be shown to undergo differentiation to insulin-secreting cells,
scientists at Harvard Medical School cultured human pancreatic ductal
cells under specific conditions, inducing the cells to form islet buds and
secrete insulin. They report:
"Thus, duct tissue from human pancreas can be expanded in culture and
then be directed to differentiate into glucose responsive islet tissue in
vitro. This approach may
provide a potential new source of pancreatic islet cells for
transplantation" ("In vitro cultivation of human islets from expanded
ductal tissue," Proc Natl Acad Sci
USA 97, 7999-8004; July 5, 2000.)
Researchers in France have found further evidence for adult
pancreatic stem cells in humans. The
pancreatic cells from healthy donors, when placed into culture,
proliferated and expressed characteristics critical for production and
secretion of insulin ("Adult human cytokeratin 19-positive cells
reexpress insulin promoter factor 1 in vitro: Further evidence for
pluripotent pancreatic stem cells in humans," Diabetes
49, 1671-1680; Oct. 2000.) The
results are another step toward treatment of diabetes using adult stem
cells.
A recent comprehensive review (1/01) in the British
Medical Journal of possible stem cell treatments for diabetes notes:
"Human pancreatic duct cells have also been grown successfully in vitro and induced to differentiate," and "Not only does the
use of adult donor ductal cells avoid the controversy of using fetal cells
but there are fewer biological problems associated with making beta cells
from duct cells than from, for example, embryonic stem cells." The authors conclude: "Of the techniques described
above, the most promising is generation of beta cells from pancreatic duct
cells. It is inherently a
shorter biological step to make a beta cell from a duct cell than it is
from other possible cells, such as embryonic stem cells and haemopoietic
stem cells" ( P. Serup et al.,
"Islet and stem cell transplantation for treating diabetes," British
Medical Journal 322, 29-32; 6 Jan 2001).
Regarding cardiac tissue, research using adult stem
cells to treat heart disease has been done with mice and in clinical
trials in humans. Adult stem
cells in mice have been shown not only to form cardiac tissue, but also to
successfully regenerate damaged heart tissue ("Bone marrow cells
regenerate infarcted myocardium," Nature
410, 701-705; Apr. 5, 2001; "Marrow stromal cells for cellular
cardiomyoplasty: Feasibility and potential clinical advantages," The
Journal of Thoracic and Cardiovascular Surgery 120, 999-1006; Nov.
2000).
In
human clinical trials, patients have been successfully treated for heart
disease using their own muscle stem cells ("Myoblast transplantation for
heart failure." Lancet 357,
279-280, Jan 27, 2001; "Doctor Puts Arm Muscle Cells Into Patient's
Heart," Associated Press, May 30, 2001; "First Percutaneous
Endovascular Case of Heart Muscle Regeneration Completed with Bioheart's
MyoCell(TM) Product," PRNewswire, May 30, 2001.)
No embryonic stem cells have ever been reported to be used in human
clinical trials.
Finally,
it is fallacious to assume that there needs to be a separate adult stem
cell for each tissue; there are numerous recent reports of adult stem
cells being transformed from one tissue type to another (e.g., bone marrow
to liver or nerve; nerve to blood). Thus
adult stem cells have the capacity to form many more tissues than the one
from which they are derived (e.g., "Multilineage potential of adult
human mesenchymal stem cells," Science
284, 143-147, Apr. 2, 1999; "Liver
from Bone Marrow in Humans," Hepatology
32, 11-16, July, 2000; "From marrow to brain: expression of neuronal
phenotypes in adult mice," Science
290, 1775-1779; Dec. 1 2000; "Turning blood into brain: Cells bearing
neuronal antigens generated in vivo from bone marrow," Science
290, 1779-1782; Dec. 1 2000; "Adult
Bone Marrow Stromal Cells Differentiate into Neural Cells In Vitro,"
Experimental Neurology 164, 247-256; Aug. 2000; "Turning Brain into
Blood: a hematopoietic fate adopted by adult neural stem cells in
vitro," Science 283, 534-537,
Jan. 22, 2000). In
this respect, adult stem cells are considered by some researchers
(including NIH funded researchers) to be pluripotent, similar to embryonic
stem cells, with the ability to form
any tissue necessary (e.g.,
"Multi-Organ, Multi-Lineage Engraftment by a Single Bone Marrow-Derived
Stem Cell," Cell 105, 369-377;
May 4, 2001; "Generalized Potential of Adult Neural Stem Cells," Science 288, 1600-1663;
June 2, 2000; Adult Rat and Human Bone Marrow Stromal Cells Differentiate
Into Neurons," Journal of
Neuroscience Research 61:364-370; Aug. 2000).
*
NIH:
"[S]tem cells in adults are often present in only minute quantities, are
difficult to isolate and purify, and their numbers may decrease with
age...Any attempt to use stem cells from a patient's own body for
treatment would require that stem cells would first have to be isolated
from the patient and then grown in culture in sufficient numbers to obtain
adequate quantities for treatment."
FACT: Research is showing these
claims not to be true. Research
from April, 2001 shows that only ONE transplanted adult stem cell may be
able to regenerate tissue in several parts of the body ("Multi-Organ,
Multi-Lineage Engraftment by a Single Bone Marrow-Derived Stem Cell"; Cell 105, 369-377; May 4, 2001).
In fact, research indicates that previously reported human stem cell
frequencies and their self-renewal activity have been markedly
underestimated and that sufficient numbers of adult stem cells can be
easily generated for clinical applications ("High marrow seeding
efficiency of human lymphomyeloid repopulating cells in irradiated NOD/SCID
mice," Blood 96, 3979-3981; Dec. 1 2000; "Ex vivo expansion of human
umbilical cord blood and peripheral blood CD34(+) hematopoietic stem
cells"; Experimental Hematology
28, 1297-1305; Nov. 1 2000).
Canadian scientists have
identified a way to make adult stem cells grow in the laboratory in much
the same way as they do in the developing human embryo.
Adult bone marrow stem cells and cord blood cells, when treated
with a naturally-occurring protein dubbed "sonic hedgehog" by its
discoverer, grow in culture similar to the way that embryonic stem cells
grow. The protein stimulates
growth of significant quantities of adult stem cells (G. Bhardwaj et
al., "Sonic hedgehog induces the proliferation of primitive
hematopoietic cells via BMP regulation," Nature
Immunology 2, 172-180; Feb. 2001
In
March 2000, researchers in Philadelphia identified the conditions to allow
large-scale expansion of adult stem cells in culture, making these cells
an almost unlimited resource. The
researchers achieved a billion-fold increase in a few weeks for bone
marrow stem cells in culture. ("Rapid expansion of recycling stem cells
in cultures of plastic-adherent cells from human bone marrow," Proceedings of the National Academy of Sciences 97, 3213-3218; March
28, 2000).
In
August 2000 research funded by the NIH itself and the Christopher Reeve
Paralysis Foundation found that adult human bone marrow stem cells can
create a "virtually limitless supply" of nerve cells ("Christopher
Reeve Paralysis Foundation Funds Breakthrough Research," Press Release
of the Christopher Reeve Paralysis Foundation, 8/14/00).
According to the published research results, the adult stem cells
"grow rapidly in culture, precluding the need for immortalization, and
differentiate into neurons exclusively with use of a simple protocol"
("Adult Rat and Human Bone Marrow Stromal Cells Differentiate Into
Neurons," Journal of Neuroscience
Research 61, 364-370: Aug. 2000).
*
NIH:
"[B]rain cells from adults that may be neural stem cells have been
obtained only by removing a portion of
the brain of an adult with epilepsy, a complex and invasive
procedure that carries the added risk of further neurological damage."
FACT:
Human neural stem cells have been isolated from other, more
accessible regions of the brain from numerous volunteers ("Isolation and
Characterization of Neural Stem Cells from the Adult Human Olfactory Bulb,
Stem Cells 18, 295-300; July 2000), and even from cadavers
("Progenitor cells from human brain after death," Nature 411, 42-43;
May 3, 2001).
The
NIH/Christopher Reeve Paralysis Foundation research demonstrates that
adult bone marrow stem cells can form nerve cells, eliminating the need to
isolate such cells from the patient's brain: "The marrow cells are
readily accessible, overcoming the risks of obtaining neural stem cells
from the brain, and provide a renewable population.
Autologous transplantation overcomes the ethical and immunological
concerns associated with the use of fetal tissue" ("Adult Rat and
Human Bone Marrow Stromal Cells Differentiate Into Neurons," Journal of Neuroscience Research 61, 364-370; Aug. 2000).
In
addition, studies with mice have shown that, given appropriate signals,
neural stem cells do not need to be removed from the brain at all for
growth. Rather, they can be
stimulated to regrow while still residing within
the brain. The re-growth could take place even in regions of the adult
mammalian brain that do not normally undergo new cell growth. The
researchers report: "Our results indicate that neural replacement
therapies for neurodegenerative diseases and CNS injury may be possible
through manipulation of endogenous neural precursors in
situ" ("Induction of neurogenesis in the neocortex of mice," Nature 405, 951-955, 6/22/00).
Again, discoveries in animal models will almost certainly lead to
applications in humans.
*
NIH:
"[I]n disorders that are caused by a genetic defect, the genetic error
likely would be present in the patient's stem cells, making cells from
such a patient inappropriate for transplantation."
FACT:
But such transplantation is exactly
what was done for three children in France, as reported in April of this
year. The infants, who had a
genetic defect that caused severe immunodeficiency disease, had some of
their own bone marrow cells removed.
The cells were cultured, the defective gene causing the immune
deficieny replaced, and the children were then treated with their own stem
cells. This experiment using
adult stem cells appears to be the first successful instance of a cure by
human gene therapy ("Gene Therapy of Severe Combined Immunodeficiency (SCID)-X1
Disease," Science 288,
669-672, 4/28/00).
Moreover,
correction of the genetic defect may not always be necessary to effect a
cure with adult stem cells. The
British medical journal Lancet
reports researchers treating systemic lupus (an incurable and sometimes
fatal autoimmune disease) using the patients' own bone marrow cells.
When transplanted back into the patients, the cells appeared to
have overcome the defect in all patients and repaired organ damage
previously considered permanent. The
scientists noted: "It is mysterious that the transplanted cells, which
have the same genetic defect that made the patients' immune cells go
wrong in the first place, did not grow up to repeat the mistakes of their
siblings" ("Treatment of severe systemic lupus erythematosus with
high-dose chemotherapy and haemopoietic stem-cell transplantation: a phase
I study," Lancet 356, 701-707,
August 2000).
Do
No Harm: The Coalition of Americans for Research Ethics rejects the course
of action taken by the National Institutes for Health to support
destructive human embryonic stem cell research.
Instead, our government should promote adult stem cell research
which protects the inviolability of individuals, rejects harming some for
the potential benefit of others, and holds as much, if not more, promise
for medical progress.
|
