Stem cell therapies hold great potential for treatment of a wide variety of human diseases including cardiac disease, hematologic diseases, vascular disease, diabetes mellitus, Parkinson's disease, and many others, and are therefore an important treatment modality to develop. Recently a type of multipotent stem cell has been developed from adult human and mouse bone marrow. These cells, termed multipotent adult progenitor cells (MAPC), can be expanded ex vivo for over 60 population doublings while maintaining telomere length and normal karyotype, and have the ability to differentiate in vitro into cell types representing all 3 embryonic lineages (neuroectoderm, endoderm, mesoderm). When injected into mouse blastocysts MAPCs incorporated and differentiated into most if not all tissue types further demonstrating their multipotentiality. MAPCs are therefore ideally suited for the development of stem cell based therapies. To advance the development of stem cell therapies, large animal models (in addition to rodent models) are needed for proof of concept experiments as well as to assess safety of the procedures. Toward this end, we have begun development of MAPC in the rhesus macaque. The rhesus macaque, by virtue of its close phylogenetic relationship with humans serves as an excellent animal model for many human diseases, and therefore, is an important species in which to develop MAPC technology. In our preliminary data we show strong evidence of having developed a rhesus MAPC line with many of the features of human and mouse MAPCs. In our first specific aim of this project we propose to expand and complete our characterization of the differentiation potential of this initial cell line by confirming RNA expression studies, assessing protein expression in the differentiated cells with immunofluorescence and Western blots, and by assessing the functional aspects of the differentiated cells. We will also compare bone versus bone marrow as a source of MAPC lines to attempt to increase the success rate of MAPC isolation, and as part of this aim will also develop additional MAPC lines.
In specific aim 2 we will examine the hypothesis that clonally-derived MAPC lines have the ability to differentiate into all 3 embryonic lineages and therefore, are indeed multipotent. Relevance: Completion of these studies will expand our knowlegde of adult stem cells and greatly enhance our ability to develop and test adult stem cell therapies for future application to human diseases.
