Fountains of Youth
Every single cell in your body "stems" from a stem cell. These are cells that have the potential to become any kind of cell: heart, lung, nerve, skin, and many others. They also renew themselves so that your stem cell supply doesn't get depleted.
You begin life as a single cell: an embryo formed by fusing your mother's egg and your father's sperm. That single cell divides into two connected cells--and if you have an identical twin, it's because the two cells separated completely. You and your identical twin are genetic clones!
These early embryonic stem cells keep dividing: Two become four, and four become eight. Up to the eight-cell stage, each cell has the potential to become a bouncy baby if implanted in a womb.
As the embryo develops, cells begin to specialize, or differentiate, based upon the cell's position. Some cells secrete signaling molecules, and other cells respond. Master switches are turned "oil" or "off" (see sidebar, "Turn It Up!", p. 35). They direct the activity of other genes or proteins. The cells differentiate, taking on jobs.
By the time you are born, most of your cells are stuck in dead-end jobs. For example, nerve cells send electrical signals and form circuits. Heart cells contract rhythmically to pump blood to all your tissues. Pancreatic cells make hormones like insulin that help to regulate blood glucose. These cells have no hope of ever doing something different.
But a tiny fraction of cells, adult stein cells, remain in the brain, hair, skin, fat, heart, baby teeth, pancreas, and bone marrow. They remain quiet. However, given the right signals--injury or growth factors--they find their way to the correct place, transform themselves into the required cell types, and begin the process of healing and growing.
Without stem cells, you'd live a very short life!
Birth of Stem Cell Research
The entire field of stem cell research started nearly 50 years ago without any fanfare. Leroy Stevens, a scientist at the Jackson Laboratory in Bar Harbor, ME, came across a lab mouse with a huge scrotum. When Stevens examined the tumor inside, he saw a mixture of tissues, including hair and teeth! Stevens had come across a rare tumor called a teratoma. He traced the origins of the teratoma to an embryonic stem cell.
Studies on mouse stem ceils (and those of other animals) are helping us to understand how they stay undifferentiated, what signals they respond to for dividing and differentiating, and how they organize themselves into tissues. We are also beginning to understand how cancers are formed because cancer cells go backward in development, becoming more and more unspecialized.
Of course, no mouse compares to a human, so scientists eager to study the details of human development and cell-based therapies for diseases have established human
embryonic stem cell lines. For this, they have used stem cells from aborted fetuses or from extra embryos made in in vitro fertilization clinics.
Stem Cell Therapies Today
The best-known stem ceil therapy has been in use for close to 40 years: bone marrow transplants. E. Donnall Thomas from the Fred Hutchinson Cancer Center in Seattle, WA, won the Nobel Prize for making bone marrow transplant an option for people suffering from some blood disorders such as leukemia or anemia.
A person suffering from leukemia gets a combination of chemotherapy and radiation to kill all bone marrow and blood cells. Next, a sample of "matching" donor bone marrow containing healthy adult stem cells--usually from a blood relative--is injected into the patient's bloodstream. In successful transplants, the stem cells migrate into the patient's bone marrow and begin producing healthy new leukocytes (white blood cells) and other blood and bone marrow cells.
Some people with severe Parkinson's disease have entered clinical trials in which they had fetal stem cells transplanted directly into their brains. Younger patients showed some improvement. In older patients (over age 60), there wasn't a significant difference in reducing the symptoms of Parkinson's. However, the stem ceils differentiated into neurons, and some even produced dopamine, the neurotransmitter whose presence in insufficient quantities can cause Parkinson's disease. Perhaps the neurons failed to make the proper connections. More experiments are underway to study how stem cells can help rebuild damaged brains.
Most stem cell therapies today rely on ceils that are donated by another person. Therefore, the donor and recipient must be compatible so that the donor cells aren't rejected by the recipient's immune system or--worse yet--actually go on to attack the recipient in what is called graft-versus-host disease.
Potential for Good
Ideally, it would be best to stimulate our own adult stem cells to repair damaged tissues. James Fallon at the University. of California in Irvine has done just that in rats! His group injected transforming growth factor- ITGF-) directly into rat brains. In healthy brains, stem cells divided and then disappeared after a few days. However, in damaged brains simulating Parkinson's, the stem cells divided, migrated to damaged areas in the brain, and differentiated into dopamine-secreting neurons. The rats regained some lost function.
There has been a great deal of excitement over recent studies showing that adult stem cells can differentiate into other types of tissues, given the right environment. Neural stem cells were coaxed into producing muscle cells, bone marrow stem cells produced heart cells, and stem cells from fat differentiated into muscle and cartilage cells!
If these cells live up to their expectations, you might one day be able to go to the doctor to have your adult stem ceils "harvested" for use elsewhere in your body. The stem ceils would receive a specific cocktail of growth hormones, and--Presto!--the cells would divide and grow into a desired tissue that doctors could then transplant back into your body. Need a new kidney? No problem. Of course, many technical difficulties need to be surmounted in determining the best ways to isolate these rare ceils and grow them in sufficient quantities for a transplant.
Today, human embryonic stem cells are easier to obtain, are essentially immortal, and can differentiate into all cell types--including heart, pancreatic, or nerve cells--spontaneously. In fact, stem cells require very specific growing conditions to keep from forming "embryoid bodies"--little clumps of ceils that organize themselves into particular tissue types.
It's not that far-fetched to think that someday we could have banks of human embryonic stem cells that would be directed to differentiate into specific cell types for transplantation into patients with Parkinson's, heart failure, diabetes, and many other diseases. Perhaps we'll even have "universal" stem cells that don't provoke the immune system.
The possibilities for stem cell therapy are exciting. Scientists need to determine the true potential and limitations of both embryonic and adult stem cells as we enter this brave new century.
The Ethics of Stem Cell Research
Any technology involved in human reproduction is controversial. Contraception, abortion, in vitro fertilization, and now stem cell research all spark debates about what human life is and the moral and legal status of the human embryo.
We must weigh the benefits versus the risks of this research, and determine as individuals and as a society whether it is the "right" thing to do. Ethical decisions are never easy.
Choose one of the following questions, and send your thoughts to "Choices." ODYSSEY. 30 Grove St., Suite C, Peterborough, NH 03458. We'll publish some of your responses in a future issue.
* Do embryonic stem cells represent a human life?
* Should "extra" frozen embryos that are created through in vitro fertilization be used to establish stem cell lines or should they be "adopted" by couples wishing to have a baby? Or both? Who should make that choice?
* Does the end (cures for debilitating diseases) justify the means (human embryonic stem cell research)?
Potent Cells
Multipotent ceils have limited potential. For example, blood stem ceils differentiate into various blood cell types. Pluripotent cells can become almost any kind of cell. Embryonic stem cells are of this type. Totipotent ceils have total potential--they can make an entire organism. In humans, cells are totipotent until the eight-cell stage.
Teratoma
--A tumor that is formed when a specialized cell becomes unspecialized to the point of becoming embryonic. Often these cells migrate to other tissues and differentiate, making kidney tubules, nerves, or
In vitro--In an artificial environment outside the human organism; In this case, eggs are fertilized with sperm inside a test tube
Leukemia--Cancer of the white blood cells, the leukocytes, which causes them to grow and divide but not fight off infection
Anemia--A condition resulting from too few red blood cells, which carry oxygen to all your tissues. Underlying causes include increased destruction of red cells, deficiencies in iron or vitamins, or cancer.
Parkinson's disease--A loss of neurons that secrete dopamine, a neurotransmitter, leading to tremors and immobility
Vijaya Khisty Bodach holds a doctoral degree in biochemistry and biophysics. She worked as a scientist for 15 years and now enjoys writing about science from her home in Redmond, WA.