Stem Cells: What Are They?

Many types of stem cells exist in the human body. All have the capacity to replicate, to self-renew; and they have the capacity to differentiate in order to produce specific body parts such as muscle cells, skin cells, nerve cells, and such. Yet scientists believe they are organized in a hierarchy according to a scale of specialization. Please watch carefully as I label the steps on the hierarchical staircase.

On the top we find totipotent (totally potent) stem cells, which are capable of forming every type of body cell. Each totipotent cell could replicate and differentiate and become a human being. All cells within the early embryo are totipotent up until the 16 cell stage or so.

Next are the pluripotent stem cells which can develop into any of the three major tissue types: endoderm (interior gut lining), mesoderm (muscle, bone, blood), and ectoderm (epidermal tissues and nervous system). Pluripotent stem cells can eventually specialize in any bodily tissue, but they cannot themselves develop into a human being.

Finally, we have tissue specific stem cells committed to making blood, muscle, nerve, bone, or other tissues. Hematopoietic stem cells, for example, are responsible for all types of blood cells, but no other tissue types. These renew themselves, yet they specialize in the tissue they produce. Their continued presence in an adult person gives the body its repairing and healing ability.

We have just made the point that tissue specific stem cells--such as those we find in the hematopoietic, intestinal, and epidermal systems--are valuable to the body because they continue to replace themselves. Yet, curiously enough, they may turn out to be even more valuable. They may be transferable. Recent experiments with mice have successfully transferred neural stems cells from the brain to the bone marrow, resulting in the production of blood. Once transplanted from the brain into the bone marrow, the neural stem cells produced a variety of blood cell types including myeloid and lymphoid cells as well as early hematopoietic cells. This shows two things. First, the neural stem cells appear to have a wider differentiation potential than is required to produce brain tissue. Second, some kind of triggering mechanism must be present in the blood system that can instruct the stem cell genes to produce blood cells. Thinking ahead medically, this brightens the prospect that neural cell transplants might be able to treat human blood cell disorders such as aplastic anemia and severe combined immunodeficiency.

Regardless of how interesting this might be, our focus here is on pluripotent cells. What Thomson and Gearhart have done is isolate pluripotent hES cells. The Thomson method is to take a human egg fertilized in vitro, which itself is a totipotent stem cell. Thomson then nurtures it to the blastocyst stage, about four to six days. He then removes the trophectoderm, the outer shell, thereby exposing the inner cell mass. He separates the cells and places them on a feeder tray and cultures them. Each cell is now pluripotent, capable of making any bodily tissue; but because the cells no longer constitute an embryo they are not thought of as potential human beings.

Gearhart arrives at pluripotent stem cells, but he takes another route. He begins with an aborted fetus at about the five to eight week stage. He removes the primordial germ cells, which at this stage still have the full complement of 46 chromosomes. Later in fetal development the gonads would otherwise become distinguished either as ova for girls with 23 chromosomes, or sperm for boys with 23 chromosomes. Prior to this stage, still at the five to eight week period after conception, the germ cells are migrating toward the genital ridge with 46 chromosomes. The Gearhart procedure catches them in this early migratory movement. Once the primordial germ cells are separated and placed on a feeder tray, they become cultured pluripotent hEG cells.

It is not yet clear whether or not hES cells are identical to hEG cells. Both are pluripotent and equivalent in function, to be sure. Yet, it may be discovered that different alleles appear in different hES cells, because hES cells could be imprinted by either the male or female source. The blastocyst stage of embryogenesis is a stage that avoids the gender imprint. What is not yet known is whether original gender imprint will matter. For the foreseeable future the two types of stem cells will be treated the same.

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