Wednesday, 3 December 2008

STEM CELLS - the Future Regeneration, Part I

As a scientist pondering over the merging of regenerative medicine and astrobionics, how could I not take a look at the advent of stem cell research. It encapsulates all that is exciting about science: it's new, it's controversial, research is increasing exponentially, the variety of applications is expanding, promises of great magnitude abound, expectations are high, and yes, there are politics and shame. But most exciting are the early successes, since these herald achievements to come. Think of powered flight. At first it was all theory and ridicule. Then a few brave pioneers risked all to prove that is was possible. And before you knew it, exponential advances (particularly through massive war-driven investment) have thus far culminated in moon landings, Mars explorers, deep space probes, the rise and fall of Concorde, and now the gargantuan people carrier, the Airbus A380. So perhaps stem cells will become another powered flight success story. What we must avoid however, is the potential run-away effect of any success. For flight it is crowded skies and pollution. For stem cells it appears to be risk of cancer and dodgy clinics offering suspect miracle cures. The problem with new biological advances is that we often get caught off guard. Let's hope therefore that we keep our eyes open with this one and not turn a blind eye to issues that arise.

OK then, let's do an overview of the basics. First we must realise the importance of understanding the principles of any new avenue of scientific research lest we misguidedly slam new advances as being unethical, dangerous, or immoral. Just look at what Darwin and Copernicus had to deal with when they upset the Church (later topic perhaps). Stem cell research is already under scrutiny, so let's see why. In essence a stem cell is rather boring and non-descript: a tiny see-through football just ticking over. When given the right chemical instructions however, this little entity will start dividing to produce new cells that have a specific function, such as a liver cell (hepatocyte) or nerve cell (neuron). This process is called differentiation. Thus the stem cell may differentiate into specific cell types. It is highly complex but the principle remains. Stem cells can self-renew and may generate many different types of cells that in turn make up the various forms of tissues that constitute the body. And hence you see a truly great potential for stem cells. One can instruct them to generate required cell types or tissues that could be used to replace damaged tissue (e.g.; from severe burns or disease) or use them to grow organs in the laboratory for transplantation and medical research.

Now the controversial bit and how we get round it. There are essentially two classes of stem cells: those derived from the early embryo (embryonic stem cells - ESC) and those found in tissues in the adult (so-called adult stem cells). An additional and very useful source of stem cells is cord blood - after a baby is born, blood can be removed from the umbilical cord and stem cells isolated from the blood and frozen for storage (cryopreservation). This process has a great advantage since cells isolated from cord blood can be used to generate tissues for that person from which the cord blood was taken, hence obviating the risk of rejection. In the early days, the majority of stem cell research was done with ESC which meant that a (usually) five-day old embryo would be required and therefore destroyed, to provide a source of such cells. Why ESC? Because they have the ability to generate any cell type (except a fertilised egg - zygote ) after all, their role is to generate a new organism. Importantly, little was known about adult stem cells either. The use of ESC in research however, is not acceptable to the pro-life group who regard even the primitive, 5-day embryo and what it represents as sacrosanct. Furthermore, there is concern that ESC could be used for reproductive cloning of humans. Perish the thought of producing more of me! One way round this problem is to use mouse ESC and indeed mouse models have helped much with our learning. They are not human of course and we still eventually need to jump to human models to verify translatability and to generate cells for therapies. The way round this is to concentrate on those stem cells that come from adult tissue (cord blood or tissues directly from the adult body).

There exist different types of adult stem cells that vary in their capacity to produce ranges of differentiated progeny. Indeed, imagine a heirarchy of stem cells in which the pluripotent ESC can produce any type of cell (although the fertilised egg is the ultimate, totipotent cell because it gives rise to ESC) and then down the tree are stem cells that can produce a broad range of other cell types (multipotent). Finally, at the bottom of the tree we find those cells that are only able to produce a few different types of differentiated progeny (oligopotent). This last type of stem cell is usually confined to a specific tissue and is responsible for generating new local tissue in response to loss from disease or injury. In the liver, for example, the local stem cell is known as the oval cell and generates the two key differentiated cells that make up the liver: hepatocytes and cholangiocytes. Nonetheless, it is likely that scientists could learn to provide the right signals to instruct such cells to revert back to an embryonic-like stem cell and therefore acquire the potential to generate any cell type from an adult stem cell. It is all down to gaining an understanding of the complex mix of biochemicals and the type of local environment (milieu) that instruct and allow the stem cell to differentiate.

We'll move on to deeper consideration in Part II.

Signing off on stem cells for now,

The Senile Scientist

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