Human Embryonic Stem (hES) cells have the capacity to become all of the cell types of the human body. However, clinical applications of these cells require an understanding of how to isolate the downstream embryonic progenitors (EPs) of specific tissues. The CPMCRI Shared Research Laboratory (SRL) proposes to utilize a new two-step single cell technique to rapidly isolate a large number of potentially useful EPs, expand the number of those cells, test them for quality, and then share those purified cell types with other medical researchers throughout California. Specifically, the SRL will:
1. Isolate uniform populations of novel EPs that can become different tissues directly from discarded human IVF embryos. Using the two-step technology, ~ 1000 novel cell lines will be isolated and analyzed for gene expression and quality, banking, and distribution.
2. Isolate uniform populations of novel EPs that can become different tissues from hES cells derived from discarded IVF embryos carrying disease genes. In collaboration with Pacific Fertility Center, embryos carrying disease genes will be used to generate hES cells or caused to change into cells that can become different tissues using the two-step technology. Novel disease-bearing EP lines will be provided to California researchers in parallel to the normal lines for drug discovery and inherited disease research.
To this end a 1500 sq/ft laboratory at CPMCRI will be renovated and dedicated as the SRL for stem cell research not sanctioned by the Federal Government. The facility will contain 3 cell culture hoods, 6 incubators, a cryopreservation system, microscopes, centrifuges, a robotics cell culture platform, and various equipment items necessary for cell culture.
The Principal Investigator will serve as the Director of the facility. A Facilities Manager will be responsible for the day-to-day supervision of the facility. Core personnel will be responsible for the culture, cryopreservation, and distribution of the cells to researchers at CPMCRI, neighboring institutions, and institutions throughout California. CPMCRI researchers have projects that include neurological disease (ALS and nerve cell regeneration), cancer (breast cancer stem cells and cell migration), cardiovascular disease (myocyte regeneration), and inherited disease-related organ repair (cystic fibrosis and sickle cell disease).
Statement of Benefit to California:
The proposed research at the CPMCRI SRL benefits the people of California by providing medical researchers in the state novel human cell lines useful in both basic scientific study and potentially for use in the treatment of numerous degenerative diseases. The CPMCRI SRL will provide its collaborators with human embryo-derived cells that are more differentiated than human embryonic stem cells, are closer in their characteristics to the actual tissue that they are intended to repair, and therefore are closer to therapeutic application. The role of the SRL at CPMCRI will be to generate, characterize, test, and distribute these cell lines derived from normal human embryos through a process of direct differentiation wherein human embryonic stem cell lines are not utilized. In addition, the CPMCRI SRL will generate EPs from embryos carrying inherited disease gene alleles. The novel method of deriving these cells and the unique genetic properties of those generated with abnormal genetic backgrounds, offer a unique service to California researchers, useful in understanding the biology of disease and early human development, cell based drug discovery, and for the cell-based treatment of degenerative disease.