Researchers at our institution are increasingly including human embryonic stem cells (hESCs) in investigations of development, regeneration and disease. A hESC shared research resource (hESC Core) will be a valuable and cost effective mechanism to enable researchers to begin work with hESCs, facilitate ongoing efforts, provide a central source for high quality established and newly-derived hESC lines that are not on the list of federally approved lines, and assist researchers with evaluation and selection of hESC lines intended for specific purposes. The facility will also provide access to specialized equipment essential for conducting experiments with hESC lines, which would not otherwise be accessible to researchers working with non-federally approved lines.
The pilot projects described in this proposal are examples of efforts employing hESCs and originate in multiple parts of the institution. Projects to understand the origins of genetic abnormalities that accumulate in hESC lines in culture will help ensure that hESC-based therapies are safe. Projects that are developing models of human cancer are creating platforms for basic studies of cancer and for discovery of novel therapies. Projects that are designing strategies for differentiation of hESCs to specific fates will make possible use of hESCs in cell replacement therapies for patients with degenerative diseases, diabetes and cancer.
The hESC Core will be responsible for maintenance and propagation of existing hESC lines and derivation of new lines using strict quality assurance. The Core will also be devoted to facilitating studies involving genetic modifications of hESCs and directed differentiation by manipulation of microenvironmental cues. These functions will be required for creation of cancer models and development of cell replacement therapies. In addition, the Core will provide space for investigators constrained by federal funding restrictions or institutional resources. The Core will also provide cells and laboratory space for researchers from neighboring California State University Campuses who have submitted projects that would use this Core and that mesh well with existing programs.
Beyond being a starting point for investigators initiating hESC-based projects and an active partner in ongoing projects, this hESC Core will be a shared resource useful to all California scientists interested in hESC research. We anticipate collaboration with other CIRM-funded hESC shared research laboratories, sharing capabilities, techniques and cell lines to maximize leverage of CIRM funds.
Statement of Benefit to California:
The hESC shared resource will play an essential role in the study of hESC biology and investigations of their utility in understanding human disease and developing new therapies. Using hESCs, COH researchers aim to minimize the tumorigenic potential of hESCs and to develop a better understanding of human cancers of the blood and brain, and to develop innovative cell replacement therapies for treatment of diabetes, hematological disorders, skeletal disease and muscular abnormalities. The hESC Core will generate new hESC lines that may be better suited to specific applications compared with existing lines, and that will be derived and maintained under conditions consistent with potential future clinical application.
COH, as a leader in hematopoietic and islet cell transplantation, has unique scientific strengths. Our HCT Program is the largest in California and is at the forefront of developing new cellular and biologic treatment for hematological disorders. We also have demonstrated leadership in selection, culture and manipulation of cells under GMP conditions for application to investigator initiated IND-based trials. Our experience and expertise in taking discoveries from bench-to-bedside places us in an outstanding position to do the same for hESC-based discoveries. This experience directly benefits the proposed hESC Core, since its efforts to maintain and derive hESC cells require strict conditions of quality assurance.
As the key resource for planned and existing research projects, the Core will facilitate entry of talented new investigators into investigations and applications of hESCs. It is important to note that this facility will serve neighboring institutions (e.g., those in the California State University system), allowing these scientists access to hESC research which is otherwise not possible. We anticipate collaboration with other hESC core facilities—sharing technologies, capabilities and cell lines to maximize the application of CIRM funds.