Stem Cell Primer I: What are Stem Cells

Stem cells are a hot political issue, but I bet less than 2% of Americans could explain just what the controversy was, what the difference between adult and embryonic stem cells is, or what nuclear transplantation is. Until recently I couldn't, and, without being cocky, if I don't understand an issue in biology, not much of the general population does.

So here is a not-so-quick primer on what stem cells are, potential uses, and the controversy over creation and use of embryonic stem cells. Upfront, I'd like to acknowledge an excellent article that appeared in the Journal of Clinical Investigation last year by Gerald and Ruth Fischbach. This is an excellent summary and not overly technical. I recommend it

What are stem cells? Stem cells have 2 essential properties. 1: they can reproduce themselves indefinitely 2: they can differentiate into more specialized cell

Remember, cells reproduce by dividing into two daughter cells, which may or may not be identical to one another. A stem cell is capable of dividing indefinitely, but often it will divide into two different (or asymmetrical cells), one that carries on as a stem cell and one that starts down the path to being a specialized cells such as a nerve or muscle cell. "Differentiation" refers to how far down the path toward specialization a cell has gone. In general, there is an inverse relation between differentiation and ability to reproduce. Fully differentiated cells like muscle cells, nerve cells, or hormone secreting cells have a limited ability to reproduce.

What is all the fuss about? Stem cells are a promising source of therapy for a variety of chronic diseases, especially those that involve loss or destructon of specific cells.

For example, Type I (aka Juvenile or Insulin dependent) diabetes mellitus is caused when the immune system destroys the beta-cells of the pancreas which secrete insulin. Insulin is required for cells througout the body to effectively take up glucose from the blood. With no insulin, the cells starve, but the glucose levels in the blood go sky high. To get energy cells must use alternative metabolic pathways which cause a varitey of problems. Currently, patients with Type I diabetes must check their blood glucose levels multiple times per day and then inject insulin. Despite this, they often develop various complications of high blood sugar levels such as damage to nerves, infections and kidney and eye damage. Too much insulin can cause life threatening low blood sugar (hypoglycemia).

An attractive alternative treatment would be replacing the pancreatic beta cells. Sometimes, a whole pancreas from a deceased donor can be transplanted into a diabetic and some success has been achieved isolating beta-cells from deceased donors and transplanting them directly into diabetics. In both cases, intense suppression of the immune system is required because the recipient's (the diabetic patient's) immune system recognizes the transplanted tissue as foreign and tries to kill it. Additionally, there are a limited number of donors available, making widespread application of either approach impractical.

An ideal solution would be to somehow regenerate beta-cells using the patients own cells as a starting material. While the immune system would still likely recognize the cells (remember they destroyed the original ones), the reaction is likely to be less intense, since at least they are derived from the patients own cells.

A stem cell would be the ideal solution. The appropriate cell could be isolated, reproduce itself indefinitely and give rise to offspring that would be (or differentiate into) beta-cells that could then be replaced in the body.

A number of other diseases would be amenable to replacement of deystoryed or worn out cells. Examples would include Parkinson's disease, spinal cord injury, and amyotrophic lateral sclerosis (ALS aka Lou Gehrig's disease).

Sounds great! Why isn't this in widespread use? Good question. Turns out stem cells are hard to find. It is not entirely clear which cells can serve as precursors for specific specialized cells (i.e. which cells can differentiate into beta-cells) and stem cells represent at most only a small fracton of cells in the body and may be in inconvenient locations (such as in the pancrease). For some cell types such as neurons it is not clear that a source of stem cells is present in adults. Also, these cells are hard to work with. They may be hard to isolate, finicky about growth conditions and prone to differentiate and lose their capacity for self renewal. So a lot of work remains to be done