A long-term objective of this research is to determine if these neural stem cells can be transplanted to treat stroke, brain tumors and neurodegenerative disorders. This capability would give physicians a renewable source of neural progenitor cells, available from a patient's bone marrow instead of the brain, and without the ethical and tissue-rejection issues associated with the use of fetal stem cells.
Results of the study appear as the cover article of the December issue of the journal Experimental Neurology. While this study was conducted in rats, similar optimistic results have been seen in human tissue, according to senior author John S. Yu, M.D., Co-director of the Comprehensive Brain Tumor Program at the Neurosurgical Institute.
Using modified viruses as transporters, researchers were able to transfer specific genes into neural stem cells – cells that have the potential to differentiate into any of several types of cells of the central nervous system. They then confirmed that the new cells expressed the proteins that had been encoded and established that the stem cells were capable of differentiating into astrocytes, neurons and oligodendroglia.
The replacement of damaged brain cells with healthy cells cultured from stem cells is considered one of the most promising therapies in the treatment of stroke and neurodegenerative disorders such as Parkinson's disease. Numerous studies are underway to develop effective methods, but finding a reliable source for the generation of neural cells for transplantation has been a challenge. The use of embryonic cells and fetal tissue raises ethical questions and the possibility of immune rejection.
Therefore, the best source of tissue for transplantation is the patient, and studies have shown that neural stem cells can be isolated, cultured and propagated from the brain tissue of adult mammals. But the removal of healthy tissue from a patient's brain introduces another set of safety, practicality and ethical issues.
The work at Cedars-Sinai involved a several-step process. Whole bone marrow cells were cultured, leading to the generation of "spheres" that were similar to neurospheres grown from neural stem cells. The bone marrow spheres were then differentiated into both neurons and glia. These cells, with their potential for expansion in the laboratory, may be good candidates for transplantation and repair of the nervous system, according to the researchers.
Dr. Yu said other recent related studies at the Institute have shown that neural stem cells are capable of tracking brain tumor cells as they spread. This is an important finding because one of the greatest challenges in treating malignant brain tumors is the fact that tumor cells often separate from the main tumor mass and migrate to form satellites. Malignant tumors also have poorly defined borders that are enmeshed in healthy tissue, making it difficult or impossible for surgeons to remove all of the cancer without damaging normal brain.
"In our research, neural progenitor cells could clearly be seen tracking pockets of tumor cells that were migrating away from the main tumor mass," said Dr. Yu. "This clearly demonstrated the ability of neural progenitor cells to actively follow pockets of tumor cells that disseminate through the brain."
Neural stem cells were also able to track brain tissue that was injured when blood flow was restricted – the type of damage caused by ischemic stroke. Forty-eight hours after neural stem cells were injected into the arteries of rats with ischemic brain lesions, researchers found transplanted cells distributed throughout the ischemic part of the brain. The cells were readily able to cross the blood-brain barrier, the body's natural defense to protect brain cells from toxic substances.
The bone marrow study was supported in part by National Institutes of Health grant NS02232 to Dr. Yu. Peter Kabos, M.D., a post-doctoral fellow at the Institute, is the article's first author.
Cedars-Sinai Medical Center is one of the largest nonprofit academic medical centers in the Western United States. For the fifth straight two-year period, it has been named Southern California's gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthrough in biomedical research and superlative medical education. Named one of the 100 "Most Wired" hospitals in health care in 2001, the Medical Center ranks among the top 10 non-university hospitals in the nation for its research activities.
Journal
Experimental Neurology