DERIVATION AND SAFETY TESTING OF NON-HUMAN PRIMATE EMBRYONIC GERM CELL LINES

Magee-Women'S Res Inst And Foundation, Pittsburgh PA

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Abstract

Two types of pluripotent stem cells, embryonic stem (ES) cells and embryonic germ (EG) cells have been developed from human and murine embryos and fetuses. ES cells are derived from the pre-implantation blastocyst whereas EG cells are derived from primordial germ cells (PGCs) in the fetal gonad. Such pluripotent stem cells are capable of differentiating into a wide variety of cell types and represent an important new resource for the treatment of human diseases. Differentiated cells produced from pluripotent stem cells could potentially be used to treat a wide variety of human diseases including Alzheimer's, Parkinson's, diabetes, stroke and heart disease. But major questions about the growth, normal differentiation, stability of genomic imprints and potential for tumor formation of stem cells need to be addressed before they can be used clinically. Technical and ethical barriers preclude many of these questions being addressed directly using human ES or EG cells. Therefore, many of these questions will need to be studied in pre-clinical animal models. Differences in the growth characteristics, marker expression and gene imprinting status of murine and human ES and EG cells suggest that mice might not represent the most appropriate model for all pre-clinical studies. Studies of ES and EG cells in primate species closely related to humans could help fill gaps in our knowledge concerning the utility and safety of cell-based therapies. Whereas ES cells have been developed from non-human primates (nhp), there have been no reports of attempts to generate EG cells from non-human primates. Here we propose to derive primate EG cells and to compare their growth, differentiation capacity and marker expression with existing primate ES cells and with human ES and EG cells. Primate ES and EG cell lines will then be used to analyze questions that cannot currently be addressed using human stem cells. These include whether such stem cells can differentiate normally into all cell lineages in the embryo, whether stem cells will form tumors upon transplantation and whether altered genomic imprints exist and if they present a significant barrier to stem cell transplantation. The goals of this proposal are designed to fill gaps in our knowledge of the usefulness and safety of pluripotent stem cells in cell-based therapies.