The overall goal of this application is to provide the opportunity for the applicant to gain laboratory skills and knowledge base relevant to stem cell research and provide a basis for further studies employing adult bone marrow-derived stem cells in animal models of human diseases. Specifically the applicant will spend one year at 100% effort in the Stem Cell Institute, University of Minnesota, under the sponsorship of Dr. Catherine Verfaillie, Director of the Stem Cell Institute. During this time the applicant will actively pursue a stem cell-related research project, participate in weekly Stem Cell Institute seminars and journal club, and attend at least one stem cell-related scientific meeting. Dr. Verfaillie's laboratory has focused on adult bone marrow-derived stem cells and, in their ground-breaking work, have recently characterized a rare population of cells from human and mouse bone marrow that has the ability to differentiate into a wide variety of tissue types including mesoderm, neuroectoderm, and endoderm, and have termed these cells multipotent adult progenitor cells (MAPC, i.e., bone marrow-derived multipotent stem cells). These cells can be expanded in cell culture indefinitely and maintain telomere length and normal karyotype. MAPC injected into early murine blastocysts contribute to most, if not all, somatic tissues thus demonstrating their multipotentiality. Such multipotent stem cells hold out great promise for treatment of many diseases, particularly diabetes mellitus, as well as Parkinson disease and many others. However, the use of stem cells for therapeutic applications will rely on testing in appropriate animal models. Toward this end the overall goals of the stem cell-related project for this proposal are to isolate, culture, and characterize MAPC from the rhesus macaque (Macaca mullata). Specifically these goals are: 1) to establish methods for the isolation, culture, and in vitro expansion of rhesus macaque MAPC (rmMAPC) based upon methods previously shown to be successful in the human and mouse; 2) demonstrate the ability of (putative) rmMAPC lines to differentiate in vitro into a wide variety of cell types representing mesenchymal, neuroectodermal, and endodermally-derived cells; and 3) determine the phenotypic characteristics of (putative) rmMAPC lines. The rhesus macaque was chosen as the model species due to its close phylogenetic relationship with humans and well characterized diabetes models in this species.
