We've got a new president who's paying attention to Real Honest-to-God Science--yay! One of the major hot-button science issues that's been dragged into the political arena over the last few years has been stem cell research. I thought it might behoove Kossacks to learn a bit about what the hell stem cells are and what all the fuss is about.
Qualifications to talk about this: I'm a science dork finishing my biology degree, and did extremely well in my stem cells course this fall.
What's a stem cell?
A stem cell is an undifferentiated cell that can proliferate and give rise to multiple tissue types from the same precursor cell. The hallmarks of "stem-ness" as currently understood are:
- Immaturity: that is, it's an undifferentiated cell typical of early development; mature tissue cells have taken a final, differentiated functional form.
- Long-lived: rather than self-destructing after a few days, like many of your cells, a stem cell hangs around for a long time.
- Capable of giving rise to multiple types of tissue
We tend to think of cells generally as being able to self-replicate in some way; that's part of what a stem cell does, but a stem cells does more than just self-renew. A stem cell can certainly self-replicate, but it also makes cells different from itself, which then makes other cells, which then become a whole bunch of other cells that end up as many different types of cell.
The most familiar example of the mechanism at work here is the regeneration of an entire blood supply via bone marrow graft. As most of you probably know, your entire blood supply is constantly replenished from proliferative cells in your bone marrow. These proliferative cells make all the many kinds of cells that your blood is made of: macrophages, T-cells, B-cells, erythrocytes, etc. Those cells in your bone marrow that are responsible for replenishment of your blood are stem cells; specifically, hematopoetic stem cells (HSCs). So yes, bone marrow transplant is a type of stem cell therapy.
What's "undifferentiated"? Exactly what you'd think it means: undifferentiated cells have not developed into mature, specific cell types. An undifferentiated cell is a little like a blob of clay before it's been sculpted into something: it has the potential to become a flower pot, or an electrical resistor component, or a floor tile, or a bust of Shakespeare. What it ultimately turns into depends on what signals it gets.
Types of Stem Cells
The research is moving very quickly, but as of right now, there are four general categories of stem cells:
- Embryonic stem cells (ES)
- Adult stem cells
- Induced pluripotent cells (iPS)
- Cancer stem cells
Let's see what each of these is.
An embryonic stem cell comes from a fertilized embryo. As you remember from high school health class, the stages of development are fertilization, which fuses genetic material from an egg (oocyte) and a sperm into a zygote; then the fertilized egg divides, begins to form differentiated tissue, and eventually you get an entire organism.
The stage of development just before differentiated tissue types begin to form is the stage at which embryonic stem cells can be extracted. The fertilized egg divides into two cells that are all identical, then into four cells, eight cells, sixteen cells - all identical to each other. In some animal studies, these cells have been removed and allowed to grow separately, and have produced complete offspring. This is also the stage at which a human zygote can become a pair of identical twins. Once you have enough cells to arrive at a ball-like structure called a morula, two cell populations exist: cells on the inside, called the "inner cell mass" or ICM, and cells on the outside. Embryonic stem cells are that inner cell mass.
After morula stage, a process called gastrulation takes place. The process is similar to what you'd see if you pressed your finger into a balloon and then pressed against one side of the inside of the balloon: your finger makes a section of the balloon where the rubber has three layers. This is basically what happens in gastrulation. Those 3 layers are the first differentiation of tissue type in development, and each layer gives rise to a different set of stuff. The layers are called endoderm, mesoderm, and ectoderm; collectively, they're referred to as germ layers.
The term "pluripotent" generally refers to cells that can cross these developmental germ layers. As you might imagine, the "-potent" part refers to what the cell has the ability to do. Other designations are "multipotent," which usually means cells that can make different kinds of tissue within a germ layer, and "unipotent," which means the cell can only make one kind of tissue.
Induced pluripotent cells (iPS) are a brand-new technology. What they are is regular adult cells that have been exposed to a variety of factors experimentally to induce them to become pluripotent. It's very difficult to get it to work at this point, and researchers are hot on the trail of what factors work and why.
Adult stem cells are those hematopoetic stem cells, for example, or some other cell that normally lives in a fully developed organism and hangs around waiting until the organism needs tissue to be repaired or replaced. There is a class of these resident in striate muscle tissue (they're called satellite cells), in two brain areas in rats (neural stem cells), and perhaps in other organs, too (some new research may be published very soon). Adult stem cells typicaly do not cross germ layers (at least not as far as we know so far).
Cancer stem cells are a hypothesized reason for why cancer occurs. If you look at what some of the characteristics of stem cells are, it starts to sound a lot like cancer: the cells proliferate, multiple tissue types form (tumors can have blood vessels), and if the cancer is the result of long-term damage, then it must be to tissue that hangs around for a long time. Like a stem cell. That's the bare bones of the idea, anyway.
Difficulties
One of the major problems with stem cell therapy is that normal stem cell functioning is so similar to cancer, and we don't yet undertand exactly what makes a proliferative cell do what it should do, as opposed to doing its own weird, pathological thing. If you induce a cell to proliferate, how do you know you didn't just start a tumor? How do you tell the difference? It's difficult, and researchers are rightly moving very cautiously.
Another huge issue is immune rejection of transplanted tissue. Yes, this happens, even to stem cells. Getting around this problem is one of the main attractions of induced pluripotent cells, or adult stem cells: if the tissue source is the patient, then you're unlikely to get an immune system response that destroys the transplanted cells. One of the trials that was recently approved will include adminstration of immunosuppressants; the idea there is that maybe that way, the immune systems of spinal cord injury test subjects won't attack transplanted therapeutic stem cells.