© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 19, 1445-1447,
October 3, 2001
© 2001 Oxford University Press
NEWS |
What Is the Promise of Embryonic Stem Cell Research?
This August, U.S. President George W. Bush made the long-awaited announcement that he will permit federal funds to support research on the approximately 60 embryonic stem (ES) cell lines already in existence as of Aug. 9.
Since then, a debate about the usefulness, quality, characteristics, and availability of the 64 ES cell lines has ensued in the scientific community, in Congress, and in the pages of nearly every major newspaper and news magazine in the country. (See related story, p. 1447.)
As the moral, ethical, and legal debates continue, the fundamental question remains: Can ES cells live up to the expectation that they will be the building block of potentially miraculous cures? What evidence exists to show that diseases such as diabetes, Parkinson’s, lupus, heart disease, and cancer will become treatable with help from ES cells? Some of the answers can be gleaned from the NIH report, Stem Cells: Scientific Progress and Future Research Directions, which was published in June (http://www.nih.gov/news/stemcell/scireport.htm).
Stem Cell Successes in the Past
One type of stem cells—hematopoietic stem cells—is being used in therapies today. These cells can be isolated from blood or bone marrow and can renew themselves, differentiating into many types of specialized cells found in blood or the immune system. These cells are used to treat leukemia and lymphoma patients by using bone marrow transplants of their own previously collected cells or the cells of matched donors.
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These stem cells, however, have limitations. They are difficult to isolate in large numbers. Advanced warning is needed to allow hematopoietic stem cells to be collected from a patient for future treatment. Patients without such warning must receive cells from a matched donor. Matching patient with donor is difficult, time-consuming, and imperfect.
While ES cells offer some clear advantages, there are many hurdles that researchers must overcome before ES cells can be used in treating any of these diseases. A major challenge is determining the most efficient and effective way to transform ES cells into the cell type desired. The proper differentiation before use is imperative because nondifferentiated ES cells have been shown to form tumors—teratomas—in immunocompromised mice.
Growth factors can be added individually or in combination to ES cell cultures to coax the cells into differentiating into specific cell types. Although ES cells differentiate spontaneously into many cell types, differentiation with growth factors result in cultures more likely to contain only one or two types of cells.
ES cells have been differentiated into cells resembling skin, muscle, neurons, cardiac myocytes, pancreatic islet cells, and cells that make up blood. Many research groups are working to define the best way to persuade ES cells to differentiate into specific cell types.
Autoimmune Diseases
Lupus, an autoimmune disease, occurs when a patient’s immune system attacks and destroys tissues and organs throughout the body. Early clinical trials are attempting to destroy the immune system and replace it with, it is hoped, a normal functioning immune system from adult stem cells harvested from the patient.
Researchers may be able to use ES cells to generate the "new" immune system from unaffected cells, which may eliminate the possibility of reestablishing the disease in the patient, the report suggests. In the future, banks of ES cell lines may allow cells to be matched to the lupus patient, limiting the possibility of rejection of the new immune system. Also, preliminary studies in mice have suggested that differentiated ES cells are inherently less susceptible to rejection than adult stem cells, which may reduce this concern for transplant recipients.
Similar methods are being investigated to treat other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, and inflammatory bowel disease.
Type I diabetes, or juvenile-onset diabetes, also an autoimmune disease, occurs when the patient’s immune system attacks and destroys the islet cells of the pancreas that normally produce insulin.
There is evidence that replacing the destroyed tissue would cure diabetes. However, because of the low number of donated organs and the risks involved in transplant operations, only 1,300 transplants occur each year. Both whole-organ pancreas transplantation and islet cell transplantation require patients to take immunosuppressive drugs for the rest of their lives. The use of genetically engineered ES cells may allow the patient to avoid the risks and inconveniences of immunosuppressive drugs.
Recent studies in mice have shown that ES cells can be encouraged to differentiate into insulin-producing cells. "Taken together, these results (of diabetes research) indicate that the development of a human embryonic stem cell system that can be coaxed into differentiating into functioning insulin-producing islets may soon be possible," the report states.
Rebuilding the Nervous System
The possibility of regeneration of brain and spinal cord tissue holds out hope for patients with Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), stroke, and spinal cord injuries.
Preliminary studies have shown that ES cells can restore movement in an animal that is partially paralyzed. In the laboratory, ES cells are pushed toward development into neural cells and grown in large quantities. The cells are then injected into fluid surrounding the spinal cords of partially paralyzed rats. Three months after the injections, many of the treated rats in a Johns Hopkins study were able to move their hind limbs and walk, albeit clumsily. The researchers found mature motor neuron-like cells derived from human embryonic germ cells throughout the spinal fluid that had continued to develop.
Researchers of Parkinson’s disease—caused by the death of dopamine-producing neurons in the brain—first realized the potential for replacing the damaged brain tissue of patients in the early 1980s. In 1998, NIH researchers were able to grow large quantities of neurons from embryonic mouse brain and relieve Parkinson’s-like symptoms in rats.
The same researchers recently have coaxed mouse ES cells to efficiently differentiate into neurons with all of the characteristics of precursors of dopamine-secreting cells. Geron Corp., Menlo Park, Calif., recently reported that their researchers had directed human ES cells to become mature dopamine-secreting neural cells in the laboratory.
Heart Disease
Hypertension, coronary artery disease, or heart attack can cause damage to cardiomyocytes, the heart muscle cells. There is still no evidence that stem cells exist in the heart naturally, but researchers have been able to push stem cells to develop into new cardiomyocytes in the laboratory. Considering the scarcity of donor hearts available to help the millions affected by heart dysfunctions, ES cells may eventually offer more hope than heart transplants.
According to the NIH report, research using mouse adult stem cells to repair damaged heart tissue in mice is promising. Stem cells appear to be able to repair many types of tissue necessary for proper function of the circulatory system. In rats, human adult stem cells have been used to form new blood vessels in areas of damaged heart tissue and when injected into the bloodstream near damaged heart, these cells can minimize the loss of cells and reduce the formation of scar tissue in the heart.
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