Stem Cell Research Affected by Government Policies

Dr. Jack Kessler has spoken on stem cell research before Congress and to audiences across the country.

In the upcoming presidential election, many issues are at stake. One that affects scientists at the Feinberg School and around the country concerns policies on stem cell research, particularly those regulating the use of embryonic stem cells. "It's absolutely essential for government policies to change for this field to progress and deliver on its promise," says Jack Kessler, MD, chair of the Ken and Ruth Davee Department of Neurology and Clinical Neurological Sciences.

Dr. Kessler, Benjamin and Virginia T. Boshes Professor of Neurology, notes that the current administration has not made embryonic stem cell research illegal—a fear some scientists have should President George Bush be reelected—but has put many restrictions on how it may be conducted. While 78 stem cell lines were approved for use in federally funded research, only 19 stem cell lines are actually being distributed, according to an article in the August 9, 2004, issue of American Medical News. Explains Dr. Kessler, "The National Institutes of Health supports this research, including my own, but only if we use those approved embryonic stem cell lines. Many other embryonic stem cell lines have been generated by universities and companies and are available for anyone to use. But we cannot use government funds to support research using those cell lines."

Types of Stem Cells

Three types of stem cells exist. "The first is the totipotent stem cell. An example is a fertilized egg in the uterus. A totipotent cell by itself can give rise to an entire embryo," explains Dr. Kessler. "The second kind is the pluripotent stem cell. A pluripotent cell cannot by itself give rise to an embryo, but it can give rise to all the different cells found in the organs of the body. An example is the embryonic stem cell.

"The third type is the multipotent stem cell. A multipotent stem cell can give rise to more than one type of cell but not all the different cells in all the organs. Examples of multipotent stem cells can be found in almost every organ of the body, including the brain, liver, bone marrow, and skin."

"It's easy to understand why we have stem cells," he continues. "For example, if you didn't have stem cells in your skin to regenerate all the different types of cells that make up the skin, you'd quickly erode it away. In the same way, bone marrow stem cells are constantly giving rise to all the cells that make up the blood because you need new blood."

Multipotent stem cells are also sometimes called adult stem cells or umbilical cord stem cells. While they are abundant in the umbilical cord blood, they are also present in the organs of newborns, children, and adults. Some populations of multipotent stem cells are more active than others, such as those in the skin and bone marrow.

Says Dr. Kessler, "One of the big surprises in the neurosciences was the discovery that the brain has many stem cells, even the adult brain, but they tend to be inactive. Only a few populations of neurons are maintained by active stem cells in the brain. Otherwise, for the most part we don't make new neurons, even though the cells with that capability are still there."

Part of the controversy about pluripotent or embryonic stem cells arises from a misconception of the word "embryonic" in this context. Says Dr. Kessler, "Embryonic stem cells are made from the blastocyst stage of development. This is a hollow ball of 100–200 cells that has no potential on its own to become a human being. It must be put into a woman's uterus before anything can happen. Simply fertilizing an egg cell in a dish does not give you a human being."

In the center of this hollow ball is the inner cell mass. In embryonic stem cell research, the inner cell mass is removed and placed in a tissue culture dish. "Stimulating the cell mass to grow and make copies of itself is called establishing an embryonic stem cell line," says Dr. Kessler. "This produces the pluripotent stem cells we are all so excited about."

The Promise of Stem Cell Research

Scientists are learning how to give stem cells the right molecular signals to transform them into specific cell types. Dr. Kessler's lab explores how stem cells can be coaxed into becoming nervous system cells. "My lab is working with both multipotent adult stem cells and pluripotent embryonic stem cells," he says. "We do not know yet which kind of cell will ultimately be necessary for which kind of clinical problem. Our goals are to devise techniques to regenerate the spinal cord after injury and brain cells after stroke."

In the spinal cord regeneration project, he is working with Samuel Stupp, PhD, Board of Trustees Professor of Materials Science, Chemistry, and Medicine and director of the Institute for Bioengineering and Nanoscience in Advanced Medicine, to combine the power of nanotechnology with stem cell biology. Dr. Stupp developed materials composed of nanofibers that can provide an extracellular scaffolding to promote healing or regeneration of specific tissues. These could potentially be designed to trigger stem cells to become spinal neurons or specific organ cells.

Stem cell biology also holds the potential for developing patient-specific stem cell lines for clinical applications. The technique used is correctly called somatic cell nuclear transfer, but is commonly referred to as "therapeutic cloning." Cloning, Dr. Kessler explains, means taking the genetic material from an adult animal cell and inserting it into a fertilized totipotent egg cell that has had its native genetic material removed. That totipotent cell is then implanted into a uterus to develop into a genetic copy of the adult animal.

In contrast, fertilized cells are not used in somatic cell nuclear transfer. "You take an egg cell—it need not be fertilized—and remove its nucleus. Then you take a cell from your patient, remove its nucleus, and place it into the egg cell. The cell is grown in culture until it reaches the blastocyst stage, when the inner cell mass is removed and cultured in a dish to establish an embryonic stem cell line," he details. "The result is a stem cell line that matches your patient so you don't have to worry about immune system rejection."

Such pluripotent cells could then be used to regenerate damaged heart cells, for example. "Sometimes patients with diabetes also develop heart disease," says Dr. Kessler. "Using pluripotent cells, you might be able to treat both the patient's pancreas and heart."

Stem Cell Research at the Feinberg School

He notes that a growing number of investigators at the Feinberg School are involved in research in stem cell biology. For example, William Lowe, MD, professor of medicine in the endocrinology division, is investigating the use of pluripotent stem cells to generate insulin-secreting cells, which could be used to treat diabetes. Robert Lavker, PhD, professor of dermatology, discovered the location of the adult stem cells that regenerate the corneal epithelium of the eye. His laboratory also studies epidermal stem cells, which play a central role in maintaining skin and repairing wounds.

Anjen Chenn, PhD, assistant professor of pathology, is investigating how neuronal stem cells give rise to the wide diversity of cells that make up the mature brain, knowledge that may lead to therapies for neurodegenerative diseases such as Alzheimer's. Cardiologist Todd Rosengart, MD, professor of surgery and head of the Cardiac Gene Therapy Laboratory at Evanston Northwestern Healthcare, is developing a way to implant bone marrow stem cells into the heart to repair scarring caused by heart attack.

Brain stem cells are the focus of studies under way in the Neurobiology Program of Children's Memorial Research Center (CMRC). For example, Francis Szele, PhD, assistant professor of pediatrics, is investigating how cells between the striatum and the lateral ventricles produce neurons and how they respond to brain injury. Mary Hendrix, PhD, professor of pediatrics and president and scientific director of CMRC, studies the ability of pluripotent stem cells to renew themselves indefinitely, which may shed light on the growth of cancer cells.

Drs. Kessler and Hendrix have played major roles in the political arena as advocates for stem cell research. They have both testified before the Health and Human Services Appropriations Subcommittee in Washington in favor of lifting some restrictions on stem cell research. They have also been active advocates in Illinois, appearing before legislators in Springfield to argue for the passage of the state's stem cell research bill, one that recently passed in the House of Representatives but fell two votes short in the Senate.

In the Division of Immunotherapy for Autoimmune Diseases, Richard Burt, MD, professor of medicine and division chief, leads a multidisciplinary clinic- and laboratory-based program developing ways to use bone marrow stem cells and immune cells to treat conditions such as lupus, multiple sclerosis, rheumatoid arthritis, and cancer.

"Northwestern Memorial Hospital has a major clinical program in bone marrow stem cell transplantation," adds Dr. Kessler. "People sometimes forget that bone marrow transplantation is a stem cell therapy that has been used for more than 20 years." Likewise, Children's Memorial Hospital has an active program in pediatric bone marrow transplantation.

These and other investigators at Northwestern and its hospital affiliates represent a "critical mass" of stem cell investigators that Dr. Kessler believes will attract "a world-class investigator to lead a full-fledged stem cell research institute." The search is ongoing for a lead scientist to head the Institute for Stem Cell Research.