DOCTOR'S VIEW ARCHIVEMedical Author: Michael Lill, M.D.
Medical Editor: Frederick Hecht, MD, FAAP
Over the last few months, there has been a lot of publicity on the subject of "stem cells". There have been reports from the National Academy of Sciences and comments have been made by the President. Regulations have been promulgated and there has been discussion of 60 stem cell lines being licensed. Speeches have been made in the US Senate and the House of Representatives and there has been much discussion about the use of stem cells to cure diseases as diverse as diabetes, Alzheimer's disease, cancer, heart attacks, and strokes .
But what does this all mean? What is a stem cell and why has there been so much fuss made about it?
Part of the difficulty with this topic is terminology. Different people are using the same term, "stem cells", to refer to vastly different things. Hopefully, by the end of this article, we will have a good understanding of what a stem cell is and what it is not.
The best and most readily understood example of a stem cell is that of the fertilized egg, or zygote. A zygote is a single cell that is formed by the union of a sperm and ovum. The sperm and the ovum each carry half of the genetic material required to form a new individual. Once that single cell or zygote starts dividing, it is known as an embryo. One cell becomes two, two become four, four become eight, eight to sixteen, and so on, doubling rapidly until it ultimately creates the entire sophisticated organism reading this article - meaning you. That organism, a person, is an immensely complicated structure consisting of many, many billions of cells with functions as diverse as those of your eyes, your heart, your immune system, the color of your skin, your brain, etc.
Embryonic stem cells
During the early stages of embryonic development, the cells remain relatively undifferentiated (immature) and appear to possess the ability to become, or differentiate, into almost any tissue within the body. For example, cells taken from one section of an embryo that might have become part of the eye can be transferred into another section of the embryo and could develop into blood, muscle, nerve, or liver cells.
If one takes cells from an embryo consisting of fewer than 1000 cells and then transfers some of these cells into a Petri dish, they can be grown indefinitely. These cells are known as "embryonic stem cells."
When embryonic stem cells are grown indefinitely in a Petri dish where they divide again and again, they are known as "embryonic stem cell lines."
It is these embryonic stem cells and embryonic stem cell lines that have received so much public attention concerning the ethics of their use or non-use. Clearly, there is hope that a large number of treatment advances could occur as a result of growing and differentiating these embryonic stem cells in the laboratory. It is equally clear that each embryonic stem cell line has been derived from the destruction of an embryo, with all the attendant ethical, religious, and philosophical problems, depending upon one's perspective.
Adult stem cells
Finally, there are adult stem cells, or committed stem cells. The adult stem cell is one of the class of cells that we have been able to manipulate quite effectively in the bone marrow transplant arena over the past 30 years. These are stem cells that are tissue specific. Rather than typically giving rise to all of the cells of the body, these cells are capable of giving rise only to the cells of a specific tissue or organ.
The best characterized example of an adult stem cell is the blood stem cell (the hematopoietic stem cell). When we refer to a bone marrow transplant, a stem cell transplant, or a blood transplant, the cell being transplanted is the hematopoietic stem cell, or blood stem cell. This cell is a very rare cell that is found primarily within the bone marrow of the adult.
Blood stem cells
The blood stem cell is capable of giving rise to a very large number of very different cells that make up the blood and immune system, including red blood cells, platelets, granulocytes, and lymphocytes. Red blood cells carry oxygen around the body and give the blood its color. Platelets are cell fragments that stop a person from bleeding and help the body to clot and heal when it is cut. Granulocytes are a type of white blood cell that help fight bacterial infection. Lymphocytes are a type of white blood cell that is part of the immune system, help fight other infections, and also may be involved in protection against cancer. All of these very different cells with very different functions are derived from a common, ancestral, committed hematopoietic, or blood-forming, stem cell.
To give you some perspective on the amount of activity that happens as a result of stem cell differentiation (turning into one of the more specialized cells of the blood), one can calculate how many cells are required or are produced by this system every day of your life. There are approximately 2-3 million red cells produced every second of your life. There are approximately 50 billion granulocytes required to fight infection every day of your life. These cells are vital to survival. Without them, you would die from anemia or infection.
The formation of mature blood cells from immature committed stem cells has been very well studied over the past 30 years. It provides an excellent paradigm, or model, for other organs.
It is now believed that all of the other organs possess similar, or committed, adult stem cells within them. Hence, there are now believed to be 20 or more different types of adult stem cells that are potentially amenable to manipulation.
One of the exciting discoveries of the last couple of years has been the overturning of a long-held scientific belief that an adult stem cell was a completely committed stem cell. We used to believe that a hematopoietic, or blood-forming stem cell, could only create other blood cells and could never become another type of stem cell. That belief is probably incorrect. There is now evidence that some of these apparently committed adult stem cells may be able to change direction to become a stem cell in a different organ.
For example, there are some models of bone marrow transplantation in rats with damaged livers in which the liver partially re-grows with cells that are derived from transplanted bone marrow. Similar studies can be done showing that many different cell types can be derived from each other. It appears that heart cells can be grown from bone marrow stem cells, that bone marrow cells can be grown from stem cells derived from muscle, and that brain stem cells can turn into almost anything.
An extended metaphor may help to illuminate this area. When I was in elementary school, I had the potential to become whatever I wanted to be (probably not an artist, but then a human zygote can't become a zebra). As I went through high school, I became more involved, or differentiated, towards biological sciences. I then went to medical school, did an internal medicine residency, followed by hematology training, and ultimately bone marrow transplant training. Currently, I am one of the most specialized specialists that you can come across.
Fifty years ago I would have stayed in that professional role for life. Now, however, I don't have to remain that way. I could be re-educated and become a history professor if I wished.
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A similar process appears to be possible for the specialized stem cells in the body. It appears that they could be reeducated and turned into something different.
There is currently much enthusiastic research being carried out in this area of adult stem cell biology. It would clearly be more attractive to be able to use adult stem cells rather than embryonic stem cells to repair patients' hearts or treat their Alzheimer's or Parkinson's disease. This is because none of the ethical, philosophical, and religious problems that arise with embryonic stem cells occur with adult stem cells.
One of the great difficulties with this entire area currently is that, first, no one is quite sure whether human embryonic stem cells and human adult stem cells are capable of being manipulated in quite the specific fashion that can be done in mice and rats. Second, it is not at all clear whether one stem cell source may be superior to the other. Hence, there is a very strong scientific need to pursue active research using both sources of stem cells.