Most normal, human cells have two copies of each chromosome – one inherited from one’s Mom and the other from Dad. Though normal stem cells have two copies of each chromosome, they can lose or gain chromosomes as they are grown in the laboratory. These abnormal stem cells are not like their normal counterparts and there is evidence that such cells might cause cancer when transplanted into patients. The development of chromosomal abnormalities in stem cells is one of the major barriers preventing the clinical application of stem cell therapies. This was demonstrated recently when the FDA suspended a clinical trial of a stem cell based treatment for spinal cord injury over concerns that the cells might have chromosomal abnormalities. Here we propose to generate stem cells that will emit a fluorescent signal when they develop chromosomal abnormalities. This way, scientists can study how the laboratory conditions in which the cells are grown influence whether or not the cells develop chromosomal abnormalities. Once we understand what causes the cells to develop chromosomal abnormalities we can grow stem cells in a manner that will prevent this, thus hastening the progress of stem cell therapies from the laboratory into the clinic.
Statement of Benefit to California:
The State of California faces immense challenges to its health care system, with soaring medical costs and an aging population. At the same time, investors are becoming more wary of funding high-risk technology development that has fueled California’s high-tech and biotech booms. The taxpayers of California have made a substantial investment in scientists who are dedicated to development of stem cell therapies that may revolutionize medicine and health care by providing new treatments for incurable conditions such as diabetes, Parkinson's disease, and spinal cord injuries. Stem cell therapies, however, are in an early stage and it is critical that research over the next few years be focused on development of cells that will be both safe and effective. A significant roadblock to progress toward the clinic is the fact that stem cells become chromosomally unstable with prolonged time in culture and such cells, when injected into patients, may cause cancer. Our current understanding of the factors that cause cells to develop chromosomal abnormalities is inadequate. We propose to develop tools that will allow scientists to monitor chromosomal abnormalities in live stem cells in a high throughput, cost effective manner. This information will be used to optimize the large-scale culture of chromosomally stable human embryonic stem cells (hESCs) for therapeutic purposes. The technology and data developed for this proposal will help to ensure that stem cells used for therapy are normal and free of chromosomal abnormalities that can cause devastating effects like cancer. We propose to develop this technology so that it can be integrated into the repertory of methods that can be used to ensure quality control and safety of cell therapies. We will make these tools available to stem cell researchers and clinicians throughout California. Ultimately, this technology will benefit California by attracting highly skilled jobs and tax revenues, and by making the State a leader in a field that is poised to be the economic engine of the future.