Heart failure may occur from a variety of causes including ischemic heart disease, toxins, pressure or volume overload. Recovery of cardiac function is hindered by a long known observation that cardiac myocytes do not divide in appreciable numbers during adult life. Physiologic demands for increased cardiac output are met by hypertrophy of existing cardiac myocytes through the formation of additional sarcomeres (the unitary contractile apparatus)within these cells. At the present time, the only remedy for end stage heart failure is cardiac transplant, which is limited by the supply of matched hearts and complicated by the need to suppress immune rejection. We have discovered a previously unknown subpopulation of stem cells in adult murine skeletal muscle that can be transformed into beating cardiomyocytes under primary tissue culture conditions. These cells are not satellite cells, myofibroblasts or myoblasts. A portion of the freshly isolated stem cells, injected into the vein of a mouse with chronic heart failure, will home to the heart and progress along a pathway to cardiac cell differentiation. In addition, we have produced a conditioned media from co-cultured bone-marrow and skeletal muscle cells that shortens the time that it takes the isolated stem cells to differentiate into cardiac myocytes. We are presently using a variety of gene array, genetic subtraction and immunologic techniques to further characterize these cells in order to facilitate the identification of human analogues. If the latter can be identified and isolated, they may be useful for therapeutic intervention in cardiac failure from a variety of causes. This would avoid the problems of immune rejection as well as the supply limitations of organ.
|Epstein, Neal D; Davis, Julien S (2006) When is a fly in the ointment a solution and not a problem? Circ Res 98:1110-2|
|Winitsky, Steve O; Gopal, Thiru V; Hassanzadeh, Shahin et al. (2005) Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro. PLoS Biol 3:e87|