Recent developments in stem cell research

BioethicsBytes Podcast September 2006 
Recent developments in stem cell research

The last week in August saw the publication of two very interesting research articles on the biology of stem cell.  One of the articles led to widespread excitement in the media, whilst the other went almost unnoticed.   I'm Chris Willmott, and in this episode of the Bioethics Bytes podcast I'm going to describe the new developments reported in those scientific papers and to explain why I believe that the press actually got excited about the wrong study. 

Stem cells, as I'm sure you know already, have been causing quite a stir over the last few years.  The attention they have attracted has resulted from both their potential in the development of new therapies and from controversy surrounding the origin of the cells.   So what exactly are stem cells and why are they considered special?  Stem cells have two properties that make them stand out from other cells in the human body.  Whereas most cells only live for a short while and then die, stem cells are capable of dividing and renewing themselves for long periods of time, potentially indefinitely.  Secondly, most cells are of one defined type and can't turn into a different sort of cell. A lung cell, for example, is distinct from a heart cell and neither can naturally turn into a different sort of cell.  Stem cells, on the other hand, have the potential to develop into a range of specialist cells.  For this reason they have sometimes been called master cells or blank cells, though neither term is ideal. As our understanding improves, the hope is that we will be able to take a stem cell, give it the right chemical guidance and cause it to become the sort of cell that has gone wrong in the patient, a process that is being called regenerative medicine.   Exactly how flexible a stem cell can be is one of the areas of controversy.  The discussion normally focuses on two types of stem cells, adult stem cells and particularly embryonic stem cells.  At 4 or 5 days after fertilisation, an embryo is made up of perhaps 100 cells and has formed two distinct layers, the trophoblast and the inner cell mass or ICM.  The trophoblast will go on to develop into the placenta, whilst the inner cell mass will become all the rest of the embryo.  As such, these ICM cells must have the potential to form any type of specialist cell, except for placenta.  It is these ICM cells that are harvested from an embryo and are then termed embryonic stem cells.  The attractive feature for many scientists is the broad potential of these cells, which are described as being pluripotent.   The controversy arises from the fact that the embryo is destroyed by the harvesting process.  This raises serious ethical issues for Christians and others who hold that the human embryo, however small, is to receive dignity and respect.  People taking this view are not necessarily opposed to stem cell research per se, many are very enthusiastic about the potential of stem cells for regenerative medicine, but they'd prefer that research was focussed on other, more ethical, sources of stem cells, such as those found in the umbilical cord after a new birth and in a variety of tissues and organs, the so called Adult Stem Cells. The existence of adult stem cells has been recognised for some time now, and there are already some well-known examples of their use in medicine.  If, for example, someone has a bone marrow transplant the key things that you are transferring between the donor and the recipient are bone marrow stem cells.  The bone marrow is the body's factory for making blood and since this is a process that has to take place all of the time, the bone marrow represents a particularly good source of stem cells.  At one time it was felt that other tissues and organs would not have their own stem cells, but stem cells have now been found in other tissues such as the gut, skin and hair that require the capability for rapid.  The search is now on for stem cells within particular organs such as the heart and the kidneys.  As well as being considered more ethically acceptable, the other advantage of adult stem cells is seen to be the potential for using a patient's own cells to treat their illness.  If this proves possible, it would bypass problems of immunological rejection that may yet hamper therapies based on embryonic stem cells. We've mentioned the fact that the bone marrow is a good source of stem cells, but it involves a pretty nasty operation to get at them.  In the perfect scenario, stem cells would be taken from an easy vantage point such as the skin or a hair follicle, somewhere that would not require an invasive operation.  These would then be cultured to turn into the sorts of cells that the patient required - be they pancreatic cells, heart cells or whatever. Given this potential, why are embryonic cells used as the workhorses of stem cell research and not adult cells?  There are, in truth, many reasons - some scientific and some political.  The main scientific reasons are two-fold.  Firstly, although adult stem cells do have some flexibility to turn into different sorts of cells, they do not share the breadth of potential specialisation demonstrated by embryonic stem cells.  As such, adult stem cells are said to be multipotent rather than pluripotent.   The second difficulty has been locating the adult stem cells within the body.  We are talking here about rare cells and looking for them has fairly been described as being like looking for a needle in a haystack.  What we need now, and what science is starting to deliver, are ways to track down these adult stem cells either through our knowledge of the exact place or niche where they might be located within a tissue or by knowing some specific biochemical marker that they have but which the neighbouring cells do not.  Sticking with the same analogy, what we need is the biochemical equivalent of a magnet to fish the needle specifically out of the hay. So, how do the two papers published last week fit into this story?  The first was a description by a team from Advanced Cell Technology in Massachusetts and published on the website of the journal Nature.  The full reference for this article and other papers mentioned in this episode can be found on our website www.bioethicsbytes.wordpress.com That's bioethicsbytes one word and bytes is spelt with a y. In essence, the Nature paper described a way to adapt an existing technology called pre-implantation genetic diagnosis, which the summary of the paper promised would allow <quote> "the ability to create new stem cell lines without destroying embryos" <end of quote>.  It was this report that received a flurry of excited discussion in the press.  So, for example, the Daily Mail described it as a major medical breakthrough and quoted University of Manchester bioethicist John Harris as saying that this was <quote> "wonderfully interesting and important" <end of quote>.   Pre-implantation genetic diagnosis, or PGD, is a technique which can be carried out in conjunction with in vitro fertilisation to check the genetic make-up of the embryo before implanting it into the mother.  When the embryo is eight cells in total, it has proven possible to roll one cell away from the rest of the cluster in order for it to undergo genetic testing.  The other seven cells seem to be able to cope with the loss, and babies have been born after this procedure with no apparent ill effect.   In the experiments described by the team from Massachusetts, individual cells were taken from a total of sixteen embryos in order to try and develop stem cell lines.  They report the successful production of two stem cell lines.   In the days following the initial publication of this report, controversy has arisen.  People have come to realise that, despite the impression given in earlier coverage, none of the embryos used in this particular research had survived.  The journal Nature took the unusual step of issuing a correction to their previous press release about the study and accusations of hype were thrown around. Now, in fairness to the authors of the research, I believe that they should be cut a certain degree of slack on this point.  Even a cursory reading of their paper indicates that they have studied 91 blastomeres - the technical name given to the individual cells in an embryo.  If they have obtained 91 cells from 16 embryos then on average the research has involved 5 or 6 cells from each embryo.  The authors comment that some of the embryos were less than perfect and I suspect that they have attempted to use all of the cells from these 16 embryos, but some of them did not survive the initial separation from the 8 cell bundles.  I'm sure too that they would argue that since this work was about proof of principle, using embryos discarded after IVF, they have obtained the maximum amount of research information from each embryo, and that these embryos were already destined for destruction.  There has definitely been some hype in the reporting of the outcome, but I don't think the blame for this lies entirely with the original team themselves.  Having said that, I do have very serious reservations about the merit of this particular line of research.  It has been fascinating to see how members of the pro-life movement and members of the stem cell research community have been strangely united in their condemnation of these experiments, albeit for very different reasons.  Christians and other who hold that even the smallest of human embryos is worthy or protection are clearly unhappy that this work has been undertaken at all.  For many of them, this approach is far from ethical, not least because the PGD process itself is most frequently used to screen for genetic conditions and embryos that do not pass muster are terminated.  Stem cell scientists are not enthusiastic about the work as they see this as an inefficient way to derive stem cells from embryos driven entirely by attempts to get around legislation in the USA, with which they do not agree. My particular quibble with this experiment is more fundamental than whether of not the work was carried out in exactly the way that the press first believed.  My difficulty is that I cannot think of any realistic scenario in which this technique is going to be a useful way to produce stem cells.  It may be true that PGD is becoming a more frequent procedure, but it is nonetheless one that is not entered into lightly - it is carried out to check a characteristic of the embryo, either for its own benefit or for the benefit of a sibling.  Under this arrangement, there is no benefit whatsoever for the embryo donating the cell - it is an unnecessary and invasive biopsy, with potential risks to the embryo.  I cannot see any parent who has had to turn to IVF to try and have a baby agreeing to put their child through the process.  The suggestion that it may be used to create a stem cell line as a back-up for the embryo itself seems equally ludicrous.  If that is the intention then why not store umbilical cord blood at the time of birth, as increasing numbers of parents are now doing? So, we turn to the second paper published at the end of August.  This article, which appeared in the journal Cell, that's C-E-L-L, described work carried out at Kyoto University, Japan.  Although, it has barely been mentioned in the general press, I believe that this study may ultimately be considered to have made significant breakthroughs in the therapeutic use of stem cells.  In an elegant series of experiments, the authors managed to take cells derived from the tail of an adult mouse and persuaded them to become pluripotent stem cells.  The researchers started by considering a total of 24 genetic factors which they suspected, on the basis of other studies, might be involved in controlling stem cells.  By missing each out in turn they identified a short list of 10 factors whose absence seemed to have a detrimental effect on cell development and they ultimately homed in on just 4 factors.  These 4 factors added together to the adult tail cells were sufficient to cause them to turn into stem cells. Now we must not get too excited, too quickly.  These new - induced pluripotent stem cells, as they have been called, were probably not as variable as embryonic stem cells and we don't yet know how to drive their subsequent development towards being any specific sort of cell that we might be wanting.  We need to recognise too that these experiments were done with mouse cells not human cells, and it is known that the control factors for stem cells are not exactly the same in mice and in man.  And finally, one of the four identified factors in regulating the conversion to stem cells is also known to play a role in cancer development if its activity gets out of control.   Nevertheless, having spelt out these various caveats, the possibility of being able to take an adult cell and turn it into a stem cell is hugely important.  Not only would this neatly side-step the concerns associated with the use and destruction of embryos, but it could also offer a way to make stem cells that are genetically identical to the.  Real clinical applications using regenerative medicine are likely to be some way off, but this Japanese result may prove to be an important step in that direction, far more so than the PGD-related approach offered by the team from Advanced Cell Technology. I'm Chris Willmott.  Thank you for listening to this bioethicsbytes podcast on recent developments in stem cell research.  If you would like to make a comment about this episode, or to suggest topics for future episodes, please contact us via our website  www.bioethicbytes.wordpress.com from which you can also find the full reference details for the articles mentioned in this podcast and some recommended resources for teaching about bioethics.  The theme is written by Matthew Stanton of stantones.net  Bioethicsbytes is produced at the University of Leicester, UK, and is supported by a National Teaching Fellowship from the Higher Education Academy.