Stem cells: Miracle or Mania?
Dr Vicky Longshaw
Space age visions of the clinical cloning of a superior race? It seems the
cutting edge technology of stem cell research is not far from a Hollywood
blockbuster. Yet the rapidly expanding global market in this research is
estimated to be worth more that $10 billion by the year 2010 (1). Exactly how
far away from an engineered race are we?
In a word: far. Horizons away. Stem cell research is like what the discovery
of penicillin was to the antibiotics industry. Revolutionary, yes. Capable of
immediate widescale use, no. We have light years of research to complete first
in order to make this technology usable in an everyday sense. But let's not get
complacent: the field is maturing at the speed of an oncoming train. This is
because the beauty of a stem cell lies in its capacity to be engineered,
something we humans are very good at. A stem cell has the remarkable potential
to develop into many different cell types in the body. In fact each of us
originated from a blastocyst: a clump of "embryonic stem cells" which
subsequently differentiated into every type of cell type required by our body, a
feature known as totipotency. And even after we reached adulthood, we retained
some of these stem cells in the form of "adult stem cells" for use as
replacement tissue throughout our lives. These adult stem cells can give rise to
any type of cell in the body except those needed to develop a fetus. In fact,
theoretically, stem cells can divide without limit for as long as the person or
animal is alive, each time dividing into daughter cells, each of which has the
potential to differentiate into a set range of other types of cell such as a
brain cell or a liver cell (a feature known as pluripotency), or to remain as a
stem cell. Our very own biological insurance policy, the value of which is only
now coming to light.
Stem cells only became available to scientists to work with in 1998 when a
group led by Dr. James Thomson at the University of Wisconsin developed a
technique to isolate and grow the cells. In the US, federal funds to support
research using human embryonic stem cells, funding on which many laboratories
are reliant, have only been available since 2001. However, in the USA, recent
private donations and non-federal government funding of $16 million and $100
million at UCSF and the University of Wisconsin, respectively, have made
possible the carrying out of expensive regenerative medicine and stem cell
research programs. And suppliers of molecular biology reagents required for such
as Invitrogen and Stem Cell Technologies have been quick to jump in and are
providing dedicated products, advice and information to stem cell researchers,
generating a whole new commercial sector.
So how do scientists go about figuring stem cells out? Pluripotent stem cells
were once-off isolated from human embryos that were a few days old, collected
from surplus embryos produced as part of In Vitro Fertilization (IVF) programs
under strict guidelines. Then these cells were used to create immortal
pluripotent stem cell "lines" which could be grown indefinitely in the
laboratory without dying, and without developing into a fetus. This provided
scientists with unlimited material to attempt to engineer into the types of
tissue that would be useful to us. Such as heart tissue for a heart transplant
or regenerative tissue for treating Parkinson's disease, diabetes and spinal
cord injuries. The potential for immune rejection of transplanted organs in
organ transplant candidates is well known and is the reason why such patients
are subjected to large doses of immuno-compromising drugs for the rest of their
natural lives. Not to mention the long waiting list for transplant organs that
are in short supply. In the face of such healing potential, who could deny the
value of future biological engineering of replacement tissue from our very own
adult stem cells, replacement tissue that has our own unique genetic stamp on it
and therefore will not be rejected by out bodies?
But does the end justify the means?
From a scientific viewpoint for a start, in order to transplant an organ into
a person, that organ must first be generated from differentiated tissue
originating from stem cells. We don't yet understand a great deal how stem cells
"know" what cell type to differentiate into. So, for example, not only
do we still have to figure out how to stimulate a clump of stem cells to
spontaneously differentiate into heart cells, but how can we be certain that all
the cells in that clump have become heart cells? What if a few decided to become
bone cells? That could be a problem.
Secondly, the global scare of mad cow disease, although in the past, is not
yet forgotten. Mad cow disease and stem cells you ask? Well it stands to reason
that any transplant organ destined for use in a human being must be guaranteed
clean of pathogens, human and animal. And what is the most commonly used,
classical reagent additive to growth media for stem cells in culture? Bovine
fetal calf serum. As yet we just do not understand what factors present in
bovine serum are required for growth of mammalian cell cultures in the lab to be
able to replace this reagent. Until we do, there are as yet no human stem cell
lines in the world that are totally free of animal derivative products. There
are consequently no laboratory human stem cell lines that any self respecting
doctor would bring near a patient.
This is why adult stem cells such as blood-forming stem cells in bone marrow
(hematopoietic stem cells) or peripheral blood stem cells are currently the only
type of stem cell used to treat human diseases. In fact doctors have been using
stem cells to treat leukemia for over 40 years, initially in bone marrow
transplants and later using more advanced techniques of collecting, or
"harvesting". Recently stem cells obtained from umbilical cord blood
have been touted as the ultimate in parental care and commercial umbilical core
blood storage clinics have rapidly sprung up. While it is certainly true that
this traditionally discarded by-product of the birth process is a rich source of
pluripotent stem cells less prone to rejection than are bone marrow or
peripheral blood stem cells, we just don't have the technology yet to generate
engineered tissue from them. And that's the rationale behind the storage
facilities: when we eventually have figured this out, those who stored umbilical
core blood will be first in line.
Legally: stem cell research for therapeutic purposes is allowed in most
places in the world, most governments drawing the line only at cloning human
embryos for reproductive purposes. On August 9, 2001, President Bush announced
the administration's position, the "Bush compromise", on embryonic
stem cell research in the US: federal funds would be approved for embryonic stem
cell research only if such research made use of existing stem cell lines.
In the UK, use of stem cells from cloned embryos for therapeutic research has
been allowed since the introduction of their Human Reproductive Cloning Act in
December 2001, which prohibits the use of human embryos for reproductive cloning
but allows the use of human embryos for research for therapeutic purposes and
the development of treatments for serious diseases.
In South Africa, there is as yet no defined legal position on stem cell
research. The closest relevant legislation the Human Tissue Act 65 of 1983 (7)
which prohibits genetic manipulation outside the human body of gametes or
zygotes. The non-binding "Guidelines on Ethics for Medical Research"
of the Medical Research Council recommend that human stem cells should only be
derived from cadaveric fetal tissue and 'surplus' embryos remaining after
infertility treatments (8).
Although most countries have now allowed the use of human stem cells for
therapeutic purposes, the next step involves strict regulation on what
scientists do. Unfortunately the much publicized scandal surrounding disgraced
South Korean stem cell researcher Hwang Woo-Suk earlier this year did much
damage to the PR of stem cell research. Hwang Woo-Suk, a professor at Seoul
National University became famous for claiming to have succeeded in creating
human embryonic stem cells by cloning, claims published in the prestigious
journal "Science" in 2004 and 2005. In fact none of the 11 customized
stem cell colonies he claimed to have created actually existed. A body blow for
stem cell research which has caused much delay in the granting of funding for
research racing to save lives.
Meanwhile in the UK, a major hotspot of stem cell research it was announced
on 7 March 2006 that Manchester will be host to a new embryonic stem cell
research initiative. This collaborative project is expected to be completed
later in the year at a cost of £2 million and will be dedicated to the
development of human embryonic stem cell lines using methods of culturing and
selecting oocytes and embryos for human embryonic stem cell derivation,
developing targets for cancer therapy and directing the differentiation of human
embryonic stem cells into lines suitable for clinical usage.
Thus although the cutting edge technology of stem cell research is not
exactly a Hollywood blockbuster, but rather a serious topic for ethical debate,
the stage is now set: Funding for stem cell research continues to flood into the
rapidly expanding global market. Proponents for embryo harvesting continue to
face delays set both by research charlatans and by the hardline opposition of
those who believe the destruction of a young life is not justified for the
preservation of an old one. However, there is no doubt that stem cell research,
especially in the use of adult stem cells is gaining in strength and popularity.
Even if we are not able to create an engineered race, our children's children
certainly will.
More information:
* Dr Vicky Longshaw is currently based at Rhodes University in South Africa
where she is a postdoctoral research fellow in the Department of Biochemistry,
Microbiology and Biotechnology.
1. lifescienceworld.com
2. www.news.wisc.edu
3. stemcells.nih.gov
4. learn.genetics.utah.edu/
5. learn.genetics.utah.edu
6. www.sciencejobs.com
7. www.mrc.ac.za/
8. www.mrc.ac.za
9. http://www.phgu.org.uk/
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