Stem Cell Research Ushers in New Era of Medicine
Maintaining Your Health on Mackinac
By Yvan Silva, M.D.

In the mid-1800s, Virchow, the noted German pathologist, determined that disease occurs at the cellular level. Since then science has progressed through many phases. This is the modern era of molecular and cellular biology, with research into the workings of the origins and development of specialized cells that form our organs and the disease processes that affect them. Transplantation of some organs as replacements is commonplace, yet research into prevention and cure of diseases at the cellular level has just begun. Custom making of tissues and organs to cure deadly diseases remains a goal that is yet elusive. Custom designs of cells to repair damage in individual patients lie at the threshold of stem cell research, the new era of medicine.

The fertilization of an ovum with a sperm, in vivo (meaning in the body) results in a cell that replicates from one to two and two to four exponentially to form an embryo. In vitro fertilization (IVF), meaning outside the body, has been conducted in the laboratory for several decades since the first "test tube" baby was conceived several decades ago. In vitro fertilization is commonplace and is used by couples unable to conceive in the usual way. These embryos are used for artificial insemination and the unused embryos are stored. It is believed that about 400,000 embryos are in storage in the United States, and three to five percent of them are designated to be discarded every year. A small percentage of parents come forward to donate their excess embryos for research, about three percent every year.

Fertilization of an egg can also be accomplished by nuclear transfer, the method for cloning. Here, the nucleus taken from an adult cell can be injected into an egg after its own nucleus has been removed. This cell can be grown into an embryo and progress to create a clone. Hypothetically, these embryos can be grown and at an optimal time stem cells can be extracted from them. These stem cells can be grown into cell lines to develop specific types of specialized cells for the specific individual. They would be patient-specific and thus there would be no threat of rejection. Since a sheep named Dolly was cloned in 1997, several animals have been successfully cloned, including mice, rabbits, cats, cattle, and most recently, a dog. Human cloning remains banned.

Embryos contain stem cells - cells that are pluripotential in that they can replicate indefinitely and can differentiate, or morph, into other cells. They are inherently capable of developing into any type of human cell. Of the billions of cells that comprise the human body, there are more or less only 200 types of specialized cells that originate and develop into the component organ systems, like the brain, heart, liver, skin, bone, and so on. And each of these cells is different from the others, although they all originate from a single embryonic stem cell line. Theoretically, an embryonic stem cell line can be developed and grown to become any of the 200-plus cell types, which then again can, under rigid laboratory conditions, be grown into healthy tissues and organs.

Umbilical cord blood from newborns is also a good source for stem cells. It is considered "adult" since cells that are contained do not come from embryos. Bone marrow transplants have been performed since 1968. Bone marrow is the progenitor of blood elements. Umbilical cord blood transplants have been done since 1988; cord blood is rich in stem cells that are capable of lodging in the bone marrow to generate blood cells and immune cells for the lifetime, unlike a blood transfusion, where the cells die in two to three months.

The adult body does contain a small number of stem cells; they are present in many tissues and organs and they lie dormant until they may become activated by injury or disease. Unlike embryonic stem cells, however, adult stem cells do not possess the potential to diversify into other types of cells. They may well be limited to becoming cells of the same organ system, for example the brain cells. Adult cells are much scarcer, they are harder to grow in cultures, and large numbers are needed to achieve desired results.

The greater potential then, in this area of research and treatment, lies in the use of embryonic stem cells. There are two sources for these, IVF and therapeutic cloning, done by nuclear transfer. In the former, scientists can take embryos donated by owners who have them stored in fertility clinics. In the latter, scientists can, for example, take a sample of skin from an individual, isolate a cell from it, and then remove its nucleus microscopically. The nucleus is then injected into an egg cell from which the original nucleus has been similarly removed. The resulting embryo is an exact genetic match of the individual.

From either source, embryos are grown and at five days the inner cell mass of the embryos, containing about 40 stem cells, is transferred to a laboratory dish lined with feeder cells. As they begin to multiply, they're re-plated onto fresh culture dishes. After several months, those that have not differentiated into specialized cells will become an "embryonic stem cell line," and these cells, in the millions, are capable of reproducing indefinitely. The challenge will be to harness these cells and direct them to specialize to form blood cells, or liver cells, or other tissues.

This challenge remains formidable. A five-day-old embryo is the size of a fine point pencil tip. The laboratory work is arduous and the complexities of genetic and chemical and growth factors and the microscopic finesse with cells are in various stages of discovery. The leap from the laboratory to human use has not yet occurred.

In 1988, James Thomson, a Wisconsin scientist, reported that he had succeeded in removing cells from spare embryos obtained from fertility clinics to develop the first human embryonic stem cell line. This discovery quickly became highly controversial because it involved the creation of human embryos that would be destroyed. Since 2001, the United States has banned government funding for this type of research, while some other countries are providing money for development, albeit with ethical oversight and tightly monitored parameters. Currently the race continues for stem cell research to benefit people with diabetes, leukemia and some cancers, heart disease, spinal cord damage and paralysis, and a host of other conditions. Research is also continuing with adult stem cells with the hope that solid progress can ensue.

A total number of 158 embryonic stem cell lines are believed to exist worldwide. The U.S. leads with about 100 lines approved for federal funding or private funding deemed suitable for research; eight other countries are actively pursuing research. The goal is to facilitate the scientific manipulation of stem cells to grow into specialized tissue cells that can be used for treatment of a variety of diseases.

Dr. Silva is a professor of surgery at Wayne State University and a resident of Woodbluff on Mackinac Island.