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Cardiac and skeletal muscle cells cease division within weeks of birth. While skeletal muscle retains the capacity for regeneration through recruitment of satellite cells, analogous populations of adult myocardial stem cells have not definitively been identified. This likely explains why damaged myocardium has limited or no ability to regenerate. Our laboratory’s goal is to understand mechanisms regulating cell division, and how such processes play a role in cardiac and skeletal muscle biology and disease. Over the past several years, the identification of heterogeneous populations of muscle stem cells in the heart and bone marrow has generated great enthusiasm for new approaches to muscle repair and regeneration. These studies also have exposed the limitations of current strategies. Direct cell replacement has been hindered by the functional isolation observed in transplanted cells. Myogenic differentiation of stem cells has been checked by a low rate of engraftment. Attempts to directly manipulate the myocyte cell cycle have been restrained by the inability of cycling myocytes to complete mitosis. Further understanding of mechanisms that govern cell cycle withdrawal and myoblast differentiation is needed to develop methods for identifying, expanding and manipulating populations of myogenic precursor cells to treat heart failure and skeletal muscle disorders. To address this need, we are studying human embryonic stem cells, as well as murine fetal, neonatal, and adult muscle stem cells, to determine their origins, factors that influence their proliferation and development, mechanisms of self-renewal, and regulation of homing to developing and injured tissues.
Selected Publications
Shen, X., Collier, J.M., Hlaing, M., Zhang, L., Delshad, E.H., Bristow, J., Bernstein, H.S. (2003) Genome-wide examination of myoblast cell cycle withdrawal during differentiation. Devel Dynam 226:128-138.
Epting, C.L., López, J.E., Shen, X., Liu, L., Bristow, J., Bernstein, H.S. (2004) Stem cell antigen-1 is necessary for cell cycle withdrawal and myoblast differentiation in C2C12 cells. J Cell Sci 117:6185-6195.
Williams, S.D., Zhu, H., Zhang, L., and Bernstein, H.S. (2006) Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes. Gene Therapy 13:837-843.
King, F.W., Nicholas, C., Leavitt, A., Reijo Pera, R., and Bernstein, H.S. (2006) Human embryonic stem cells expressing green fluorescent protein differentiate into mature cardiomyocytes. Ped Res E-PAS2006:59:5150.8.
Information last updated April 2007
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