The promise of stem cell research

Stem cells are relatively undifferentiated cells, that is, they have no specific tissue function. They are capable of self-renewal or of being stimulated to develop into specialized (differentiated) cells.

There are two kinds of stem cells: adult and embryonic. Adult (somatic) stem cells are found in a variety of mature tissues. They repair those tissues when stimulated by tissue damage. Even brain tissue contains stem cells that can regenerate neurons and other brain cells.

Human embryonic stem cells can be derived from a blastocyst. The blastocyst is a microscopic hollow ball of cells. It develops four to seven days after fertilization of an egg by sperm. The blastocyst is about the size of a period ending a sentence. It has no heart, no nervous system nor other adult tissues. Its “inner cell mass” of about 30 cells can be cultured in dishes to divide into millions of embryonic stem cells. If allowed to clump, they form embroid bodies that differentiate spontaneously into many different tissue cell types, e.g., muscle, nerve, skin. However, with specific stimuli, they can be trained to differentiate in vitro (outside the body) into a specific tissue. When implanted in vivo (inside the body) into a specific tissue, embryonic stem cells can differentiate into those tissue cells.

Embryonic stem cells provide important advantages over adult stem cells. First, embryonic stem cells are pluripotent, that is, they can form any adult tissue except placenta or fetus; adult stem cells can form only the parent tissue or very few others. Second, embryonic stem cells can be cultured in vitro to generate millions of stem cells needed for replacement therapy. Adult stem cells are rare in number, difficult to isolate and cannot be cultured. Finally, unlike embryonic stem cells, adult stem cells can accumulate genetic abnormalities.

However, embryonic stem cells could be rejected by the recipient’s immune system. This problem could be circumvented through therapeutic cloning in which the nuclear DNA from a patient’s cell is transferred into an egg cell which has had its nucleus removed. This process generates a perfect genetic match of the patient.

Human embryonic stem cells were only detected in 1998 and the ban on federal funding has deterred major research. Nonetheless, animal experiments have led to encouraging results. For example, Parkinson’s, which afflicts 2 percent of people over 65, is a progressively degenerative disease leading to loss of muscle control. It is caused by a deficiency in dopamine production in the brain. Embryonic stem cells can be transformed into dopamine-producing neurons.

Early studies showed that mouse embryonic stem cells could replace neurons and other cells of damaged nervous tissues and improve locomotion. Promising results with other organ systems include heart and blood vessels, kidney tubules and pancreatic islet cells which produce insulin.

Many technical hurdles must be overcome before embryonic stem cells will be available for human therapies, but the potential rewards are enormous.

— David Kennell (kennell@borcim.wustl.edu). The writer is professor emeritus of molecular microbiology at Washington University School of Medicine in St. Louis, Mo.