Antibodies and peptides reactive with human embryonic stem cells, either differentiated or undifferentiated, are important tools that enable the identification, isolation and characterization of specific cell types. Antibodies and peptides that detect specific proteins on the surface of human embryonic stem cells allow the characterization and comparison of different human embryonic stem cell lines and enable the isolation of defined populations of live cells. Furthermore, understanding the differences between normal cells and embryonic stem cells in their responses to oncogene activation will also help discern whether stem cell therapies would have a cancer-inducing side effect. Previous studies have disappointingly only utilized monoclonal antibodies (mAbs) targeting antigens raised against human EC cells and mouse embryos.
In this application, we propose the development of antibody reagents and peptide tools specific for human embryonic stem cells which will greatly increase the safety of future stem cell based therapies. To this end, our overall objective in this research proposal is the identification of a panel of human and mouse antibody reagents and peptide tools that specifically bind and internalize to/into live hESCs, by targeting different molecular features differentially expressed on undifferentiated hESCs. Key features of this proposal are 1) our expertise in antibody and peptide phage display methodology, 2) the capability for the generation of innovative antibody conjugates as required for successful applications, 3) a highly collaborative scientific network that has been assembled, and 4) an ability to timely evaluate the efficacy of the prepared antibodies and peptides.
Statement of Benefit to California:
Health care needs are unlimited, whereas resources are finite. Public expenditures on health care have to compete with other societal priorities such as education, the environment, defense and infrastructure. Even in relatively wealthy, developed countries, scarcity is the defining characteristic of resource allocation problems. Therefore, new therapies are desperately needed to enhance medical treatment options, to improve our quality of life and to lower healthcare costs. California has a large and diverse population that poses challenges for the future of medical care. A major goal for California’s supporters of stem cell research is the development of stem cell-directed tools/reagents that have broad medical applications. Stem cells have the potential to improve the health of all Californians, but they are especially important for research and the development of treatments for disease states that currently have no cure. For example, neurological diseases are especially difficult to treat with classical medicines, and these diseases are becoming increasingly prevalent, hence an ideal target for stem cell research.
This proposed project is designed to generate materials of natural origin as a source of new tools and reagents for the analysis and discovery of human embryonic stem cells. The development of new therapeutics/drugs will depend on further characterization of these cells and the development of assays that allow for the evaluation of well defined molecules that can identify, and potentially monitor human embryonic stem cells.