Derivation of New Human Embryonic Cell Lines in Full Compliance with Current FDA Regulatory Guidance

Funding Type: 
SEED Grant
Grant Number: 
RS1-00434
ICOC Funds Committed: 
$0
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
The research we propose develops improved safety procedures for the establishment of new human embryonic stem cell lines to treat disease. Although it addresses critical safety concerns necessary to move these cells into the realm of human disease treatment, this work could not be funded currently by the federal government. Human embryonic stem cells are used by scientists to study basic questions about biology and how cells and tissues grow. There is also much hope that these same cells will eventually be used also to treat patients. To achieve safety when it becomes possible to use them to treat patients, the collection and handling of cells must be very different from the way the same cells would be handled if they were to be used only for laboratory study. The work we propose is intended to make a complete assessment of safety practices in the way embryonic stem cells are presently handled from the time they are donated to the time they are cultured and frozen for future use. By making this study, we will be able to identify ways to improve safety. We will do this by observing the Food and Drug Administration's regulations for safety in using cells that are intended for use in treating human disease. At the present time, safety procedures are not well developed and it is crucial that they be greatly improved before embryonic stem cells can be used to treat human disease. We believe that these studies will both make stem cells safer to use for people and make such uses for people available more rapidly.
Statement of Benefit to California: 
The research we propose is concerned with developing improved safety procedures for the establishment of new human embryonic stem cell lines to treat human disease. Although it addresses critical safety concerns necessary to move these cells into the realm of human disease treatment, this work could not be funded currently by the federal government. When the voters of California approved Proposition 71, they anticipated that research done under its funding would lead to treatment of human diseases and to economic benefits to California's citizenry, although it is understood that much more basic research is also needed before this is to happen. Our work will pave the way for treatment of any human disease using embryonic stem cells by making a detailed and comprehensive study of safety procedures needed for the establishment of new embryonic stem cell lines. The currently approved federal cell lines have both biologic and safety limitations. Therefore, it is critical that new stem cell lines are established in full compliance with existing FDA safety regulations. A method to accomplish this has not yet been devised and we propose to address this barrier to safety and clinical use of human stem cells to treat diseases. This work will benefit California directly because the state will become known as the first to comprehensively address the safety issue. In addressing this issue, the clinical use of stem cells anticipated by Cailfornia's voters will be greatly facilitated while simultaneously being made more safe. In this environment, it will also become more likely that additional biotechnology companies, whose business models will be based on cellular therapy with stem cells, will be established and thrive in the state. these companies will pay taxes and provide employment.
Progress Report: 
  • A central goal of our CIRM SEED proposal was to use innovative unbiased approaches to discover novel proteins that turn genes on or off in pluripotent stem cells. An understanding of what are these proteins that act as genetic switches and how they function is of significant importance to efforts to use pluripotent stem cells to model disease states in the lab or to provide a source of cells of therapeutic interest for transplantation. We have been successful in our efforts, in that we identified a novel protein that appears to play an unexpected role in the regulation of gene activity in pluripotent stem cells. In addition, we have identified another protein that is critical to maintain the DNA of pluripotent stem cells is a state accessible to other proteins. Our research is therefore providing an integrated picture of what are the genetic switches that turn genes on or off in pluripotent stem cells, what genes do they regulate, and how is their access to DNA regulated. Some of our results have recently been published, while other research is ongoing. In parallel, we have been very successful at transferring expertise to the biotechnology sector in California. In particular, two highly qualified lab members accepted senior scientist positions at top biotechnology firms in California (iPierian and Genentech).
  • A central goal of our CIRM SEED proposal was to use innovative approaches to discover genes that control human embryonic stem cells, with the idea that this knowledge may lead to improved methods for growth and/or differentiation of human pluripotent stem cells in a clinical setting. In the past year we have continued to make significant progress on these efforts. We have found a factor that acts to turn other genes on or off and is active in embryonic stem cells. We have put a considerable amount of effort into optimizing methods to identify exactly what genes this factor controls. Our results show that this factor directly regulates pluripotency-associated genes. This is remarkable, since this factor had not to date been implicated in the regulation of pluripotency. These results put us in a position to characterize the function of this factor in embryonic stem cells in greater detail. In addition, we are applying knowledge gained from our studies to develop methods to enhance the ease with which human pluripotent stem cells are propagated. Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, are notoriously more difficult to grow than their mouse counterparts, and this has significantly hampered the ability to use existing human pluripotent stem cells to model disease. We have developed conditions that facilitate the propagation of human pluripotent stem cells in a state that resembles mouse ES cells, where they are easier to propagate and grow more rapidly. These findings, while preliminary, suggest that we have the opportunity to explore a transition of human pluripotent stem cells to a state that is easier to culture and manipulate genetically. Thus, the CIRM SEED award has allowed us to discover a novel regulator of pluripotency genes, and to develop conditions that may lead to improved culture and manipulation of human pluripotent stem cells.

© 2013 California Institute for Regenerative Medicine