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A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration.

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OHSU is an equal opportunity affirmative action institution.

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Cell Res. Wu, S. M. et al. Sci. The group of Nadia Mercader from the Institute of Anatomy at the University of Bern has been interested in understanding the cellular mechanisms of heart regeneration during the last 10 years. PubMed  The researchers teamed up with the Interfaculty Bioinformatics Unit at University of Bern, EMBL (Heidelberg, Germany), CNIC (Madrid, Spain) and the Hospital Universitario La Paz (Madrid, Spain). Circulation 100, 193–202 (1999). Science 331, 1078–1080 (2011). 93, 32–39 (2003). Sandstedt, J., Jonsson, M., Lindahl, A., Jeppsson, A. CAS  Circulation 120, 1513–1523 (2009). Relative roles of direct regeneration versus paracrine effects of human cardiosphere-derived cells transplanted into infarcted mice. Stem Cells 25, 1136–1144 (2007). We are sorry, but there is no personal subscription option available for your country. Although researchers have discovered that these heart muscle cells are re-generated by cardiac stem cells located in microscopic niches throughout the heart, these stem cells are unable to replace and regenerate nearly enough heart cells after catastrophic cardiac cell death that occurs with heart attacks. An international research group led by Prof. Nadia Mercader of the University of Bern now shows that certain heart muscle cells play a central role in this process.

335–355 (Raven, 1979). Jopling, C. et al. C.E.M. Nature 464, 606–609 (2010). Circ. Cell Cardiol. At the Center for Regenerative Medicine, we are working toward an actual cure for heart failure by regenerating lost heart muscle cells and eliminating the need for life-long treatments with expensive drugs and devices.

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This work was supported by grants from the US National Institutes of Health. Invest. CAS  Res. Circulation 118, 649–657 (2008). Functional cardiomyocytes derived from human induced pluripotent stem cells. J. Cardiol. Messina, E. et al. Pathol. A. Bergmann, O. et al. Rumyantsev, P. P. in Growth and Hyperplasia of Cardiac Muscle Cells (ed. Ther. Res.

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95, 911–921 (2004). & Mummery, C. L. Human embryonic stem cell-derived cardiomyocytes and cardiac repair in rodents. CAS  PubMed Google Scholar. Development. Zebrafish are extremely well suited to study organ regeneration. Incl. Variability of the cardiomyocyte ploidy in normal human hearts. 72, 19–44 (2010). Thomson, J. Nature Med. PubMed  While basic and clinical trials have shown that autologous stem cell therapy to replace heart cells after heart attacks has been safe in almost every instance, the benefit has been only modest because very few of the stem cells administered to the heart engraft within the areas of cell death or infarction. Stud. Heart Regeneration Heart attacks, the number one cause of heart failure, are caused by a sudden catastrophic death of hundreds of millions of heart muscle cells – functioning cells that cannot be replaced by the normal healing process. We have discovered safe, simple, inexpensive methods to enhance engraftment that then create a multitude of new contracting muscle cells. & Molkentin, J. D. Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair. Google Scholar. Chen, S. L. et al. Cell Stem Cell 7, 618–630 (2010). However, recent studies have shown that cardiomyocyte proliferation is a mechanism of cardiac growth and regeneration in animals. Pfister, O. et al. Mauro, A.) To obtain Cardiomyocyte cell cycle activation improves cardiac function after myocardial infarction.
& Sheikh, S. P. Murine 'cardiospheres' are not a source of stem cells with cardiomyogenic potential. Res. 50, 1884–1893 (2007).

Google Scholar. Madden, L. R. et al. Nature 473, 326–335 (2011). Unfortunately, there has been relatively little support for the use of a patient’s own cells to cure heart failure – regenerative medicine does not fit traditional research and development funding paradigms that support drug and device research. During their brief residence they appear to release growth factors that enhance original cells to improve healing, but the effect is insufficient. Sci. After birth, however, human heart regeneration becomes limited to very slow cardiomyocyte replacement. Moretti, A. et al. Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy. Res. Differentiation 76, 958–970 (2008). Once this concept can be successfully demonstrated, it could change the future for thousands of patients suffering heart disease and change the way heart attacks are treated. Heart failure is the leading cause of death worldwide. Circ. Developmental origin of a bipotential myocardial and smooth muscle cell precursor in the mammalian heart. Eur.

Stud. Using transgenic tools, Marcos Sande-Melón, lead author of the study and colleagues could identify a small subset of cardiomyocytes in the zebrafish heart, marked by sox10 gene expression that expanded more than the rest of myocardial cells in response to injury. & Kuhn, B. Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Possible relevance for heart regeneration in humans. 317, 188–194 (2010). J. Nature 410, 701–705 (2001). Am. Isolation and expansion of adult cardiac stem cells from human and murine heart. Toma, C., Pittenger, M. F., Cahill, K. S., Byrne, B. J. PubMed PMID: 31540899. doi: 10.1242/dev.167692. Google Scholar.

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