The research proposed has two complementary goals. The first goal is to elucidate the biological properties of adult stem cells (ASCs) that renew human tissues. The second is to translate human ASC discoveries into advances in cellular medicine. For decades, lack of critical knowledge about ASCs has been a formidable wall at the frontier of ASC research and cellular medicine. Three intractable research challenges form this wall. Methods for exact identification of ASCs are lacking, ASCs are difficult to produce in large quantities, and, therefore, important biological features of ASCs remain obscure. To address these challenges, during the past 14 years as a principal investigator, the applicant undertook research with genetically-engineered mouse cells that modeled essential unique properties of ASCs. These properties are asymmetric self-renewal and immortal DNA strand co-segregation, two defining features of ASCs. A series of reports from the applicant?s laboratory established the relevance of discoveries made with the mouse ASC models to rodent ASCs in vivo. These discoveries established an innovative foundation for identifying ASCs, expanding ASCs in culture, and investigating ASC cellular and molecular properties. With NDPA support, the applicant will change the direction of his research program, forged with rodent ASC studies, to focus on human ASCs and their conversion into embryonic stem cell (ESC)-like cells. Human ASCs responsible for liver, hematopoietic cells, pancreas, and hair will be the focus of research with the goal of developing both pre-clinical and clinical applications for cellular medicine. The applicant?s research program enjoys collaborations with several laboratories from diverse scientific disciplines and technological fields, including mathematics, chromosome biology, mass spectrometry, bioinformatics, genomics, electrical engineering, computer sciences, and the cell products industry. These interactions will complement research to expand selected human ASCs, develop tools for their exact identification, and advance ASCs as effective cellular medicines for human disease.
