stem cells

stem cells unspecialized human or animal cells that can produce mature specialized body cells and at the same time replicate themselves. Embryonic stem cells are derived from a blastocyst (the blastula typical of placental mammals; see embryo ), which is very young embryo that contains 200 to 250 cells and is shaped like a hollow sphere. The stem cells themselves are the cells in the blastocyst that ultimately would develop into a person or animal. "Adult" stem cells are derived from the umbilical cord and placenta or from blood, bone marrow, skin, and other tissues. The similar embryonic germ line cells come from a fetus that is 5 to 9 weeks old and are derived from tissue that would have developed into the ovaries or testes.

Medical researchers are interested in using stem cells to repair or replace damaged body tissues because stem cells are less likely than other foreign cells to be rejected by the immune system when they are implanted in the body. Embryonic stem cells have the capacity to develop into every type of tissue found in an adult; germ line cells and adult stem cells are less versatile. The processes that control such development, however, are not understood at present. Stem cells have been used experimentally to form the hematopoietic (blood-making) cells of the bone marrow; heart, blood vessel, muscle, and insulin-producing tissue; and sperm cells. Embryonic germ line cells have been used to help paralyzed mice regain some of the ability to move. Since the 1990s umbilical cord blood stem cells have sometimes been used to treat heart and other defects in children who have rare metabolic diseases and to treat children with certain anemias and leukemias. It has been shown that stem cells from this blood can migrate to damaged tissues and repair them.

Human stem cells have typically been extracted from surplus fertilized embryos produced during in vitro fertilization procedures. Some experimenters, however, have used embryos that were fertilized especially to produce stem cells. In so-called therapeutic cloning a nucleus from a patient's body cell, such as a skin cell, would be inserted into an egg that has had its nucleus removed to produce a blastocyst whose stem cells could be used to create tissue that would be compatible with that of the patient. Such a procedure was reported in 2005 to have been successfully undertaken in part by South Korean researchers who produced stem cell lines using genetic material from patients, but the data was subsequently shown to have been fabricated. (It was later determined, however, that the laboratory had produced stem cells using an egg that had developed through parthenogenesis , which does not involve fertilization or result in a viable human embryo.) Because extraction of embryonic stem cells destroys the embryo, the use of embryonic stem cells has been opposed by opponents of abortion . Japanese researchers used viruses in 2007 to transfer genes to human skin cells and induce those cells to become stem cells, and U.S. researchers have used similar induced stem cells in mice experimentally to treat sickle-cell disease.

The first embryonic stem cells to be isolated were extracted by British researchers from mouse blastocysts; the first human stem cells isolated and cultured were extracted by American scientists in 1998. In 1994 a National Institutes of Health (NIH) panel argued that creating human embryos for use in certain experiments might be justified, but Congress subsequently enacted (1995) a ban on federal financing for research involving human embryos in reaction to that report. The Dept. of Health and Human Services ruled in 1999, however, that that ban did not apply to financing work with stem cells, and guidelines for financing such research were issued by NIH the next year.

President George W. Bush , who had campaigned against financing embryonic stem cell research, announced in Aug., 2001, that he would support federal funding of research with embryonic stem cells, but only with the estimated 60 stem cell lines then existing. Some scientists challenged the assumption that these 60 stem cell lines would be sufficient for experimental and therapeutic needs, while others said the figure included some stem cell lines that had not yet been determined to be viable. In fact, in 2004, there were only 15 approved stem cell lines available to researchers funded by the U.S. government. The restrictions have not prevented other researchers, in the United States and elsewhere, from developing new embryonic stem cell lines and undertaking research with them using private funding, and California voted (2004) to create a $3 billion fund to underwrite embryonic stem cell research. A federal legislation that would have expanded the number of stem cell lines available for federally funded research was vetoed by the President Bush in July, 2006.

See also fetal tissue implant .

stem cells are ‘uncommitted’ cells, capable of dividing to make more stem cells, or, under appropriate conditions, to produce the kinds of specialized cells that make up the tissues and organs of the body.

A newly fertilized egg is the ultimate stem cell. It is totipotent – capable of generating all the different types of cells found in the body, and also the fetal part of the placenta and supporting tissues. The fertilized egg splits into two, and those into four, and so on. For the first few divisions, up to at least the 8-cell stage, all the cells of the tiny embryo are totipotent stem cells. Indeed, if these early cells separate, they can each continue to develop, making identical twins, triplets, quadruplets, etc.

About four days after fertilization, the route to commitment starts. Some cells form an outer layer, which becomes part of the placenta, while others make the inner mass, which is the beginning of the true embryo. Initially this consists entirely of pluripotent stem cells, which cannot give rise to placental tissue but can make any component of the fetus itself. As the embryo grows, and the parts of the body start to emerge, the individual stem cells within each future organ or tissue become further specialized so as to be capable of producing only a certain range of possible final cell types. These stem cells are then called multipotent. At a certain stage in the development of each ‘family tree’ of cells, one or both of the daughter cells produced by the division of a stem cell becomes ‘committed’, that is, incapable of further division. These committed daughters continue to differentiate and become the normal functional cells of the heart, skin, brain, kidney, and other organs.

Adult animals still have some multipotent stem cells, especially in tissues such as skin and blood, in which cells last only a short time and have to be replaced. Indeed, even in the adult brain, previously thought to be incapable of making new nerve cells, there are populations of stem cells, which are constantly producing relatively small numbers of new neurons.

We now stand at the threshold of a potential revolution in medical treatment for diseases and disorders in which organs stop working properly. At present, some such conditions, such as heart, kidney and liver disease, can be treated by transplantation of a replacement organ from another person. But demand for donor organs is far outstripping supply, and the failure rate of such surgery is quite high, mainly because of the problem of rejection. Many other disorders, such as stroke, diabetes and Alzheimer's disease, cannot presently be treated by transplantation. The great hope is that suitable stem cells, produced in large quantities through cell culture methods and injected into failing tissues and organs, will produce fresh, replacement cells to take over from lost or damaged ones.

Stem cells for such replacement therapy could be produced in a number of different ways. Ultimately, it might be possible to make them with the kind of methods used to produce the first cloned mammal, Dolly the sheep. An ordinary specialized adult cell from the patient could be used to produce a totipotent stem cell by removing the nucleus (with the DNA-containing chromosomes), and inserting it into a human egg from which the nucleus has been removed. But there are many problems with this approach, not least the fact that adult cells may have accumulated genetic errors, which will be transmitted to the stem cells produced. Everyone agrees that formidable technical obstacles must be overcome before the cloning of stem cells from adult cells becomes safe. There is also concern that the development of methods for therapeutic cloning would inevitably lead to the production of whole human beings, who, like Dolly, are genetic replicas of an adult. At present, the vast majority of scientists and clinicians, not to mention ethicists and politicians, are opposed to such reproductive cloning, but it must be said that resistance may decrease if the techniques involved can be made more reliable.

In principle, some of the patient's own stem cells could be harvested (most likely from bone marrow or certain parts of the brain), multi-plied in culture and injected into a diseased or damaged region to produce new cells. Stem cells derived from the patient's own body would have the great advantage that they would not be rejected. This approach has already been successful in experimental animals, with stem cells from bone marrow used to replace damaged heart muscle. It may soon be used in humans to treat heart disease, diabetes, and other such diseases. However, it would not be appropriate for the replacement of tissues that are diseased because of a genetic disorder (such as Huntington's disease or cystic fibrosis), since stem cells from the patient would have the same genetic mistake in their DNA. This strategy would also be inappropriate in acute conditions, demanding immediate treatment, because of the time needed for stem cells to multiply in culture.

The most immediately promising strategy is to isolate pluripotent stem cells from human embryos just a few days after fertilization, to culture them, and to inject them into the patient's diseased or damaged organ. Since such cells carry different DNA from that of the patient, they could be used to treat genetic disorders. On the other hand, this means that precautions would have to be taken to avoid rejection.

Transplantation of immature nerve cells and stem cells from the brains of aborted human embryos has been used for several years to treat the degenerative brain condition, Parkinson's disease, with reasonably encouraging results. Such treatment has not greatly alleviated the characteristic tremor of the hands, and some patients have developed disturbing unintended movements. But most have regained the ability to initiate and control their actions. It is probable that embryonic stem cell injection will soon be used in efforts to treat the degenerative diseases Huntington's disease and Alzheimer's, and even stroke, in which parts of the brain are destroyed becomes of interruption of the blood supply.

There is wide agreement among medical scientists that research on human embryonic stem cells is an important first step towards stem cell therapy, even though it may eventually be possible to use adult stem cells. Yet the prospect of harvesting cells from living human embryos smacks of Frankenstein or Brave New World, and ‘pro-life’ religious groups have mounted stout moral opposition. However, it would not be necessary to fertilize additional human eggs specifically for such research. Present methods for the production of ‘test-tube babies’ involve the production and storage (by freezing) of several fertilized eggs, the unwanted ones simply being destroyed or permanently stored. These surplus eggs could, with parental agreement, provide a ready source of embryos for stem cell collection. Moreover, as long as there are strict limits on the time for which the embryo is allowed to develop, it will have no nervous system or other organs, no possibility of feelings, and nothing approaching an independent life. Also, the indubitable suffering of the many people who might be helped by stem cell therapy ought to weigh heavily in the complex moral equation.

In 2001, the British government authorized stem cell research on human embryos up to 14 days post-conceptual age. Given the huge potential benefits of stem cell therapy, it is likely that other nations will follow suit.

Colin Blakemore

Bibliography

Further reading: Thomson, J. et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147.
US National Institutes of Health website. Stem cells: a primer. http://www.nih.gov/news/stemcell/primer.htm

stem cell A mitotically active cell that serves to replenish those that die during the life of a metazoan organism (somatic stem cell) or that produces a continuing supply of gametes (germinal stem cell).