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Submission to the Senate
Community Affairs Legislation
Committee Concerning the
Research Involving Embryos and
Prohibition of Human Cloning Bill
2002
Matthew Downey BSc(Hons)
Home: (07) 3391 0775
Work: (07) 3391 0775
37 Salstone Street
Kangaroo Point QLD 4169
Introduction
Debate surrounding the use of embryonic stem cells for medical research
purposes has generated immense public debate. The raft of opinions and
emotions raised by this controversial issue is justifiable considering what is at
stake.
For medical researchers the use of embryonic stem cells represents an area
of research which has the potential to quickly advance our understanding of
developmental biology, create a safer method for assessing drug toxicity and
provide a means for developing cures and/or therapies to treat some of the
most debilitating and fatal of human diseases and conditions. Similarly, the
people and subsequent families affected by these afflictions also have a
vested interest in seeing this potential realised.
With the current governments’ emphasis on promoting biotechnology
research and the infrastructure and economic environment in which this
research can be commercialised, the income derived from patents and other
intellectual property rights surrounding the use of embryonic stem cell
technology could be considerable.
Despite these scientific, humanitarian, and economic considerations, it is the
ethical aspect of embryonic stem cell research which is causing the most
confusion and consternation among all Australians, the members of the
federal House of Representatives and Senate included.
Ethical
considerations have been raised by almost every religious group and also by
those who lack any religious affiliation. Personally and collectively we are
being asked to answer questions which challenge our definition of human life
and the value we place on our human existence. The reality of the situation is
that we are approaching a period in human history in which we will possess
the knowledge and technology to manipulate life as we know it at the most
basic and fundamental of levels. Our responsibility therefore is to ensure that
we use our intellectual and creative abilities to create a world in which future
generations exist and flourish like none previous.
In order to make a well considered and informed decision, a thorough and
objective consideration of the facts must be made separate from the emotion
and opinion in which these facts can, either intentionally or unintentionally, be
distorted. In this submission I will present a brief review of some of the facts
concerning the research into spinal cord regeneration and place this within the
context of the current and potential contribution of stem cell research.
Spinal Cord Injury (SCI)
Approaches to treating SCI
Surgeons who treat people with spinal cord injury (SCI) are interested in three
things with regards to spinal cord regeneration: what can be done to minimise
neurologic injury, what can be done to enhance neurologic function and what
can be done for the patient with longstanding paralysis? (Kwon and Tetzlaff,
2001).
In terms of preserving nerve cell function and thus minimising neurologic
injury, considerable work on the movement of various ions across nerve cell
membranes has suggested the local application of substances antagonistic to
the movement of these ions may assist in preserving nerve function (Kwon
and Tetzlaff, 2001).
Failure of SCI patients to regain motor function has been attributed,
conceptually at least, to two apparent characteristics of central nervous
system (CNS) nerve cells:
1) the injured nerve cells have a limited intrinsic capacity to regenerate, and
2) the nature of the environment in which these cells must regenerate is not
permissive of such growth (Kwon and Tetzlaff, 2001).
As a consequence, research has focussed on characterising the intrinsic
regenerative ability of CNS nerve cells, augmenting the nerve cells’
regenerative ability and characterising the inhibitory nature of the CNS
environment (Kwon and Tetzlaff, 2001). Cellular transplantation attempts to
overcome this inhibitory environment and promote functional regeneration
(Kwon and Tetzlaff, 2001) and it is here that research into stem cells finds its
application.
Cellular transplantation
As stated by Kwon and Tetzlaff (2001), the primary candidates for use in
cellular transplantation strategies include neural stem cells, fetal cells,
Schwann cells and olfactory ensheathing cells (OECs).
Adult Neural Stem Cells
Research has revealed that the mouse adult brain and spinal cord contain
neural stem cells that can generate many of the cells required for normal
neurological function (Clark et al., 2000). Studies utilising developing chick
embryos have demonstrated that mouse-derived adult neural stem cells are
also able to give rise to various cell types that contribute to the generation of
several tissues and organs (Clarke et al., 2000). Similar experiments are yet
to be performed using human adult neural stem cells however experiments in
which human adult CNS stem cells have been cultured indicate that these
cells exhibit the capacity to generate various cells types (Temple, 2001).
While it has been noted that there exists no evidence for the ability of adultderived stem cells to make the types of nerve cells observed in the embryo,
this observation must be qualified by the fact that with reference to SCI
studies, research involving stem cells and other multipotent cells is still in the
preliminary stages (Temple, 2001).
Embryonic Neural Stem Cells
Transplantation studies involving the grafting of fetal human brain-derived
stem cells to rat or mouse brains has demonstrated widespread incorporation
in the brain of these cells and the production of various primary nerve cells
(Temple, 2001).
While both adult and embryonic stem cells offer hope with regards to
developing therapeutic treatments for SCI, extensive and comprehensive
research into the basic biology of these cells needs to be done before we can
even begin to contemplate developing applications for human spinal cord
regeneration. In contrast the results obtained from the use of olfactory
ensheathing cells (OCEs) are far more promising and have been identified as
the best option in terms of “bridging” descending and ascending neural
pathways in the damaged spinal cord (Lu and Ashwell, 2002).
Olfactory ensheathing cells (OECs)
Despite residing in the CNS, OECs are derived from the olfactory placode
which is found in the nasal cavity (Lu and Ashwell, 2002). OECs exhibit a
number of functional attributes including:
1. the ability to migrate over long distances in the adult brain,
2. the ability to provide a matrix amenable to the growth of nerve cells and
3. the secretion of chemicals which promote nerve cell growth (Lu et al.,
2002).
All of these functions combine to make OECs, and related olfactory
ensheathing glia (OEGs), prime candidates for applications in spinal cord
regeneration. OEGs derived from the primary olfactory bulb of rats have been
shown to promote nerve cell regeneration in the transected rat spinal cord
(Ramon-Cueto, 1998).
Similarly, human-derived OECs have been
demonstrated to exhibit properties similar to their rat counterpart including
extremely high viability in tissue culture and the ability to regenerate damaged
nerve cells (Barnett, 2000). The most important discovery to date however
has been the report that transplanted OEGs collected from adult rats have
lead to functional and structural recovery following complete spinal cord
transection (Ramon-Cueto, 2000).
Conclusion
In summary it can be said that research into both embryonic and adult derived
stem cells has yielded important information regarding the nature of these
cells with respect to developing therapies for the recovery of patients from
SCI. The priority of research into stem cells at present is to characterise basic
stem cell biology in terms of their role in developmental biology. This
fundamental research will aid more progressive research which aims to
understand aspects of stem cell biology which impact, in this instance, on
treating people with SCI. While research using animal models has revealed
similarities/differences and perceived advantages/disadvantages between
adult and embryonic-derived neural stem cells I believe that one overriding
consideration needs to be kept in mind. The ability to treat a person with
tissues derived from their own body will circumvent the considerable problems
associated with transplanted tissue rejection. In my opinion this fact alone is
reason enough to concentrate our efforts on understanding and developing
technologies associated with adult-derived neural stem cells in the treatment
of SCI.
Despite stem cells displaying such potential for the development of clinical
therapies for SCI, the reality is that this potential is already being realised
using OECs and OEGs. Research is also rapidly progressing into the
chemical factors associated with promoting nerve cell regeneration in the
hostile environment of the severed spinal cord. To set stem cell research
within an appropriate context, it is envisaged that future therapies will
incorporate all these areas of research and their effectiveness will be
enhanced by the synergy of these combined fields. This wholistic approach
emphasises the fact that advances in stem cell research can only be exploited
if concomitant advances occur in related fields. Regardless of the potential
exhibited by the use of stem cells in concert with other regenerative
strategies, it is suffice to say that the initial advances in treating patients with
SCI may in fact lie in developing neuroprotective methods which preserve and
promote native nerve cell function by maintaining existing nerve cell function
and preventing cell death (Kwon and Tetzlaff, 2001).
References
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L T, Papanastassiou V, Kennedy P G E, Franklin R J M. Identification of a
human olfactory ensheathing cell that can effect transplant-mediated
remyelination of demyelinated CNS axons. Brain 123; 1581-1588.
Clarke D L, Johansson C B, Wilbertz J, Veress B, Nilsson E, Karlstrom U L,
Frisen J. Generalized potential of adult neural stem cells. Science 288; 16601663.
Kwon B K and Tetzlaff W. Spinal cord regeneration from gene to transplants.
Spine 2001;26(24S); S13-S22.
Lu J, Ashwell K. Olfactory ensheathing cells their use for repairing the injured
spinal cord. Spine 8: 887 –892.
Ramon-Cueto A, Cordero M I, Santos-Benito F F, Avila S. Functional recovery
of paraplegic rats and motor axon regeneration in their spinal cords by
olfactory ensheathing glia. Neuron 25; 425-435.
Ramon-Cueto A, Plant G W, Avila J, Bunge M B. Long-distance axonal
regeneration in the transected adult rat spinal cord is promoted by olfactory
ensheathing glia transplants. The Journal of Neuroscience 18(10); 3803-3815.
Temple S. The development of neural stem cells. Nature 414; 112-117.