Adult-derived stem cells from the liver become myocytes in the heart in vivo

Recent evidence suggests that adult-derived stem cells, like their embryoni c counterparts, are pluripotent. These simple, undifferentiated and uncommi tted cells are able to respond to signals from their host tissue microenvir onment and differentiate, producing progeny that display a phenotype charac teristic of the mature cells of that tissue. We used a clonal stem cell lin e (termed WB-F344) that was derived from an adult male rat liver to investi gate the possibility that uncommitted stem cells from a nonmyogenic tissue source would respond to the tissue microenvironment of the heart in vivo an d differentiate into cardiac myocytes. Male WB-F344 cells that carry the Es cherichia coli beta -galactosidase gene were identified in the left ventric ular myocardium of adult female nude mice 6 weeks after transplantation. We confirmed the presence of a rat Y-chromosome-specific repetitive DNA seque nce exclusively in the beta -galactosidase-positive myocytes by polymerase chain reaction and fluorescence in situ hybridization. Immunohistochemistry , using a cardiac troponin T-specific monoclonal antibody,and ultrastructur al analysis confirmed a cardiac myocyte phenotype of the stem cell-derived myocytes, The beta -galactosidase-positive myocytes ranged from < 20 film t o 110 mum in length. The longer of these cells contained well-organized sar comeres and myofibrils, and formed intercalated disks and gap junctions wit h endogenous (host-derived) myocytes, suggesting that WB-F344-derived myocy tes participate in the function of the cardiac syncytium, These results dem onstrate that adult liver-derived stem cells respond to the tissue micro-en vironment of the adult heart in vivo and differentiate into mature cardiac myocytes.