A dynamic area in biotechnology today is stem cell research. Stem cells are the precursor cells of every tissue in the body and thus, have the potential to provide replacement tissue for diseased and damaged organs. Our studies on stem cell differentiation suggest that adult and embryonic stem cells share a similar tissue potential. Specifically, we believe that stem cells from adult mammalian bone marrow have the capacity to give rise to all mesoderm derived tissue-although this potential is never realized in the normal adult environment. Initial studies have shown, for example, that hematopoietic stem cells (HSCs) from adult bone marrow-which normally give rise to the cellular components of the blood-can develop into cardiac myocytes under conditions developed for nondifferentiated embryonic tissue to undergo cardiac differentiation. As a first demonstration of our hypothesis on the broad potential of adult stem cells, we propose to extensively study the formation of cardiac tissue from adult mouse bone marrow stem cells. The experiments outlined in this project are designed to: (I) definitively identify this cardiac competent cell population of the bone marrow, (II) examine the capacity of this bone marrow cellular subpopulation to maintain their cardiac competence following their expansion in culture, (Ill) investigate their capabilities as cardiac cells, and (IV) examine their ability to integrate into adult cardiac tissue as functional cardiomyocytes. The development of methods to manipulate stem cell potential will have significant future medical impact, as it will provide the means to convert stem cells to pure populations of individual cell types for replacement tissue.