http://www.actionduchenne.org/r-nav/299.jsp Blog concerning Terry Partridge Blog http://www.actionduchenne.org/blog/299/36/Stem-cells-and-muscular-dystrophy <p>Every few weeks or so, there is a report of a new stem cell that will cure a whole range of diseases.&nbsp; The more responsible of these reports include a statement that it will be some years before any actual therapies are available. It should also be pointed out that development of a practical therapy within the foreseeable future is far more likely in some tissues than in others.&nbsp; The reasons for thinking this are discussed below.</p><p>The first problem lies in making sure that the stem cells turn into the cell type in which we are interested: in the case of DMD we want them to turn into the cells which construct and repair skeletal muscle. These are called myoblasts.&nbsp; Myoblasts that can enter a resting state, so as to be available for repairing our muscles throughout life, are called satellite cells and these do seem to be a sort of stem cell that is largely restricted to making muscle.&nbsp; If we start with stem cells that can make a wider range of tissues - any tissue in the case of embryonic stem cells &ndash; then we need to be sure that we can turn them into muscle stem cells very efficiently and that none of them remains in an &lsquo;undecided&rsquo; state where it might produce a cancer.&nbsp; It is this second point that is difficult &ndash; it only takes one cell to cause a tumour.</p><p>We can also learn a lot from the tissues in which stem cells work well.&nbsp; In fact stem cells capable of replacing the bone-marrow cells that make all of our blood cells have been in use for many years. More recently skin stem cells&nbsp; have been used to replace skin in severe burns patients and earlier this year, a patient&rsquo;s own genetically modified skin stem cells were used to correct a genetic disease of the skin.&nbsp; In both cases, the tissue being treated, is one in which stem cells are in constant use for its day-to-day maintenance and so have in place mechanisms for incorporating these stem cells without any need for special tricks on our part.&nbsp; Unfortunately, most other tissues use stem cells far more rarely or possibly not at all once we have stopped growing.&nbsp; Muscle appears to be one of these tissues in which the stem cell population is rarely called into serious action. The satellite cells in muscle seem capable of doing quite a good repair job but it is not perfect and each time they are called into action the repair is not quite as good as the last time.&nbsp; These defects build up over time and the muscle gradually loses its ability to work efficiently.&nbsp; However, if we could replace the satellite cells of a DMD boy with cells carrying a good copy of the dystrophin gene, then the muscle they repaired would not&nbsp; break down and need repairing so often. <br />Perhaps the big problem with using stem cells on muscle is that we cannot deliver them very accurately to the places in which they are needed.&nbsp; The stem cells of the bone marrow work well because they pass through the blood and home to the right places.&nbsp; Skin stem cells can be delivered fairly easily to the parts of the body surface where they are needed.&nbsp; When we transplant myoblasts they do not move more than a few millimetres from the site of injection and so are very difficult to deliver to even a proportion of the body musculature.&nbsp; What we need is a muscle stem cell that we can put into the blood and that can get out into the regions of&nbsp; muscle where it is needed for repair. Up to now the only stem cells that have been demonstrated to be capable of doing this at all efficiently are the Mesoangioblasts being studied by Cossu&rsquo;s group in Milan.&nbsp; These may be the same as some other muscle stem cells but they are the only ones that have been demonstrated to be distributed via the blood.&nbsp; The fact that they can do this is more important than whether or not they are stem cells.&nbsp; There remain some questions about mesoangioblasts: in particular they do not seem to replace the satellite cells in the muscle and so would have a limited period of effectiveness.&nbsp; Also, their behaviour is different in the two species in which they have been studied. In the mouse they mostly enter the muscles immediately downstream in the artery into which they were injected whereas in the dog they seem to escape this local trapping and become distributed more generally around the body.&nbsp; How they will behave in man, remains to be seen.&nbsp; There are advantages and disadvantages to each pattern of behaviour. If they are trapped in the muscle immediately downstream of the injection site, it means that they would have to be administered separately to all of the main muscle groups of the body.&nbsp; If they distribute more broadly, then we may worry about where they get to apart from the muscles and whether they could do any damage if they lodged, for instance, in the brain or the kidneys.<br />As an overall message, matter of whether this, that, or the other cell is a stem cell, is less important than whether the tissue we are targeting has in place the mechanisms to incorporate them properly and efficiently into its structure.&nbsp; More effort is need on the development of this aspect of stem cell therapies.</p><p>&nbsp;</p> Mon, 10 Dec 2007 21:26:19 GMT http://www.actionduchenne.org/blog/299/36/Stem-cells-and-muscular-dystrophy 2007-12-10T21:26:19Z