Human Adult Stem Cell Research Break Through
Recent studies have demonstrated the widespread distribution of a population of cells in the human body which has the potential to renew themselves as well as provide many other cell types. These "adult stem cells" or "progenitors" have the potential to provide populations for cell replacement therapy for degenerative diseases and trauma repair. Although stem and progenitor cells are found throughout the nervous system, their locations require highly invasive surgery for their harvest which greatly diminishes their utility. In contrast, the tissue responsible for the initial detection of smell, the olfactory neurosensory epithelium (ON) is accessible through endoscopic surgery and contains progenitors or stem cells that account for its life-long renewal of neurons and ensheathing cells. These stem or progenitor cells when isolated in the culture dish, exhibit very high levels of cell division and contain proteins that are characteristic of progenitors that form cells of the nervous system. They form multicellular spheres in culture dishes which because they contain nestin a neural stem cell marker protein have been called neurospheres. Through their publication in 2001, Dr. Roisen's laboratory was the first in the world to report the development of methods for the isolation and growth of these human neurosphere forming cells from postmortem olfactory tissue. Working with Dr. Welby Winstead, the results have been extended successfully to patients undergoing elective nasal sinus surgery who volunteered for the endoscopic biopsy. Collectively more than 75 different patient-specific lines of neurosphere forming cells have been established from females and males with an age range of 33-97. These unique cells divide every 18-20 hr demonstrating an almost unlimited regenerative capacity; one of the cell lines has been maintained for over two and a half years in culture without degeneration. Studies by a graduate student, Charles Marshall, have demonstrated that these cells retain their proliferative and metabolic activity irrespective of the age, sex or time the cells are maintained in the culture dish. Another student, Dr. Manal Othman, demonstrated that new neurosphere populations could be grown from a single cell. This "clonal expansion" further demonstrated an important characteristic of progenitor and/or stem cells and provides evidence that large numbers of cells can be obtained from an initial very small sample. As neural progenitors these cells have shown a tendency to become nerve cells. This default can be enhanced by signal molecules that have been shown to regulate neuron development in embryonic animal models. A former graduate student, Dr. Xiaodong Zhang, used transcription factors (little genes) to induce the formation of cells that produce the myelin covering around the nerve cell processes (oligodendrocytes). These studies suggest that the olfactory progenitors isolated and maintained by Dr. Roisen's team could be used to restore myelin lost as a result of physical trauma or neurodegenerative condition such as Multiple Sclerosis. A similar molecular approach has shown that these unique human progenitors can be directed to develop into dopamine producing neurons suggesting their possible future use in the treatment of Parkinson's disease. The team is actively exploring the utility of olfactory-derived progenitors in the treatment of spinal cord injury. When the group transplanted cells into a rat spinal cord injury, the cells facilitated neuronal rescue and increased axonal regeneration over 14 weeks. Animals that could not walk across a rope because of the injury, were able to cross without difficulty 12 weeks after the cells were transplanted into the injury site (film clip available upon request)!

The studies by the University of Louisville researchers including, Drs. Fred J. Roisen, Kathleen Klueber, Chengliang Lu and Welby Winstead and their students, highlight the unique potential of adult human olfactory epithelium as a source of autologous progenitors (stem cells) for repair of spinal cord injuries and neurodegenerative diseases in the absence of immunosuppression and ethical controversy. Furthermore these cells can also provide human neural populations for pharmacological, diagnostic or genetic evaluation.

Supported by a grant from the NIH 992558 and funds from the Kentucky Spinal Cord and Head Injury Research Trust.