POSSIBLE LIMITATIONS
3.10 Even if much of the potential of adult stem cells is realised,
there are circumstances where they are unlikely to be useful.
The isolation of some types of adult stem cells for therapy, for
example the isolation of neural cells from a patient's brain,
would be impractical. Similarly, where a person suffers from a
genetic disorder or some types of cancers, adult stem cells isolated
from that individual will retain the damaging genetic alterations
underlying the disease and so be of little therapeutic value.
3.11 If adult stem cells are to be of general utility,
it will be necessary to learn how to isolate them, grow them in
culture and differentiate them into new cell types. The isolation
and growth of adult stem cells have to date proved very difficult.
Stem cells generally represent a very small proportion of cells
in adult tissues. Unambiguous identification is difficult as their
presence in a tissue or mixture of cells is generally inferred
from a research observation rather than indicated by any specific
biochemical marker which might aid their purification.[23]
Although there are several reports of "enrichment"[24]
of adult stem cells, there are few, if any, reports of adult stem
cells being purified to homogeneity (i.e. where no other cell
types are present). It has been suggested that some adult stem
cells retain many of their characteristics only as a result of
the presence of signals from other surrounding cells, and that
maintenance in culture may therefore be difficult.
3.12 Current understanding of the potential of adult
stem cells for redifferentiation is still very limited. Although
many studies suggest that such processes occur, there is often
a degree of ambiguity, for example whether or not the multiple
new cell types arise directly from a single adult stem cell with
increased potential for differentiation, or from several different
stem cells each with a limited but different potential for differentiation.
Moreover, it is not yet known whether adult stem cells give rise
to cells of different tissue types by transdifferentiation, or
by dedifferentiation to a pluripotent cell, which then differentiates
into the new cell types (see Box 2).[25]
The control and safety of dedifferentiation is a major challenge
and one about which little is yet known (see paragraph 3.18).
3.13 The efficiency of differentiation of transplanted
adult stem cells is, to date, very poor. For example, although
transplantation of bone marrow into mice suffering from muscular
dystrophy can lead to new, repaired muscle fibres, the efficiency
is several orders of magnitude below that which would be therapeutically
useful. Much research is still required to determine whether the
efficiency can be enhanced.
3.14 In their natural location in the body adult
stem cells do not exhibit great potential for differentiation
into new cell types but have evolved to give rise only to specific
cell lineages. Indeed, if they exhibited increased potential or
plasticity in their natural position in the body this would have
disastrous consequences: the "wrong" cell types might
develop into the "wrong" tissues. The feasibility of
manipulating adult stem cells to undergo dedifferentiation and
redifferentiation along pathways which they do not normally exhibit,
and the consequences of doing so, are as yet uncertain.
Do developments on adult
stem cells make research on ES cells unnecessary?
3.15 Research on adult stem cells is at a very early stage. Without
a great deal of further research it will not be clear to what
extent their therapeutic potential will be realised, or for what
type and proportion of potential applications adult stem cells
will be applicable. Although almost all the scientists who gave
evidence to us were excited by recent studies on adult stem cells,
most sounded a note of caution: many of the published studies
are still open to multiple interpretations or require replication;
and there are many crucial scientific issues to be resolved.
3.16 We received evidence from a number of individuals
arguing that recent developments in research on adult stem cells
demonstrated their therapeutic potential and made research on
ES cells unnecessary.[26]
However, the evidence from the great majority of scientific and
medical research organisations, and the experts on adult stem
cells whom we consulted, did not support that view. They did not
see adult stem cells and ES cells as alternatives but as complementary
pathways to therapy. They argued that relatively little is yet
known, and that substantially more research on both adult and
ES cells is needed before the best routes for therapies can be
ascertained; that, despite increasing optimism, it is still not
known to what extent it will be possible to exploit adult stem
cells therapeutically and in the meantime other avenues should
not be closed off; and that, even if much of the potential of
adult stem cell-based therapies is realised, it is unlikely that
adult stem cells will fulfil all therapeutic needs.
3.17 Although adult stem cells may ultimately fulfil
many therapeutic needs, the strong weight of evidence is that
the full potential of adult stem cell research and its therapeutic
application is unlikely to be realised without research on ES
cells. This is because, apart from CNR, ES cells provide the only
realistic means at present of studying the mechanisms and control
of the processes of differentiation and dedifferentiation. If
stem cell therapies (whether using ES or adult stem cells) are
to be of clinical benefit and of demonstrated safety, a much clearer
understanding of these processes is required. The utility of ES
cells for studying them is clearly demonstrated by advances made
from animal studies. Most future studies probably can and will
be undertaken using mouse (or other animal) ES cells rather than
human ES cells. Nevertheless, if safe and reliable therapies are
to be developed, a comparison with human ES cells must eventually
be made.
3.18 ES are needed for this purpose, partly because
of the relative ease with which they can be isolated, maintained
in culture and differentiated into other cell types; and partly
because they are the only fully undifferentiated pluripotent cell
type available for study. If scientists are to dedifferentiate
adult stem cells to pluripotency, prior to redifferentiation into
a new cell type for therapeutic purposes, they must know whether
they have done this correctly and whether the process is safe.
Differentiation involves "marking" the genetic material
in a number of ways. These "markings" (including chemical
changes to the DNA and the interaction of specific proteins with
it) are "remembered" during cell division. If an adult
stem cell is to be dedifferentiated prior to redifferentiation
for therapeutic purposes, these markings must be correctly erased.
In fact it is not fully established that CNR produces complete
differentiation and erasing of these markings, as recent discussion
of Dolly the sheep illustrates.[27]
3.19 It may be that, in time, scientific understanding
of the processes involved and developments in the manipulation
of adult stem cells will make research on ES cells redundant.
The Committee is not convinced that this point has yet been reached
or will be reached in the near future. These issues were exhaustively
considered in the United States last year by the National Institutes
of Health. Its comprehensive report reviewed the state of the
science as at 17 June 2001.[28]
Emphasising that ES and adult stem cells are different, its concluding
paragraph reads:
Predicting the future of stem cell applications
is impossible, particularly given the very early stage of the
science of stem cell biology. To date, it is impossible to predict
which stem cells—those derived from the embryo, the foetus,
or the adult—or which methods for manipulating the cells,
will best meet the needs of basic research and clinical applications.
The answers clearly lie in conducting more research.
3.20 Because of the importance of this issue we also asked a number
of internationally renowned adult stem cell experts for their
views. We received replies from Professor Helen Blau, of the Stanford
University School of Medicine, Dr Jonas Frisen, of the Karolinska
Institute, Stockholm, Professor Nadia Rosenthal, of the European
Molecular Biology Laboratory, Monterotondo-Scalo, and Professor
Angelo Vescovi, Director of Research at the Stem Cell Research
Institute, Milan. They are published in the volume of evidence
(pp 472-478). They were unanimous that there was a need for research
on both adult and ES cells. Dr Frisen expressed his view as follows:
My opinion is that adult stem cells are
clearly different from ES cells, and that there are no scientific
data suggesting the opposite. Although I believe everyone would
agree that it would be very good if adult stem cells had the same
potential as embryonic, this is unfortunately today only wishful
thinking. I find it very important today to work on both embryonic
and adult stem cells. This will ensure that potential therapies
are not delayed.
3.21 Of all the scientific issues relevant to our inquiry we have
given more attention to recent developments in adult stem cell
research than to any other. Scientific developments in this field
are so rapid that it is difficult to make any firm predictions
with confidence. This in itself suggests that avenues of research
should not be closed off prematurely.
Conclusions
3.22 Based on the evidence we have heard our conclusions on the
research and therapeutic potential of ES cells and adult stem
cells are as follows:
