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Your Heart, CARDIAC HEALTH & STEM CELLS

Definition of Heart Disease.

Wikipedia states: Heart disease or cardiopathy is an umbrella term for a variety for different diseases affecting the heart. As of 2007, it is the leading cause of death in the United States,[1][2] England, Canada and Wales, killing one person every 34 seconds in the United States alone.

The umbrella term "heart disease" includes the following disorders (with links to Wikipedia)

Articles

Stem-cell-based therapy and lessons from the heart

Robert Passier, Linda W. van Laake & Christine L. Mummery
NATURE|Vol 453|15 May 2008|doi:10.1038/nature07040Download

The potential usefulness of human embryonic stem cells for therapy derives from their ability to form any cell in the body. This potential has been used to justify intensive research despite some ethical concerns. In parallel, scientists have searched for adult stem cells that can be used as an alternative to embryonic cells, and, for the heart at least, these efforts have led to promising results. However, most adult cardiomyocytes are unable to divide and form new cardiomyocytes and would therefore be unable to replace those lost as a result of disease. Basic questions — for example, whether cardiomyocyte replacement or alternatives, such as providing the damaged heart with new blood vessels or growth factors to activate resident stem cells, are the best approach — remain to be fully addressed. Despite this, preclinical studies on cardiomyocyte transplantation in animals and the first clinical trials with adult stem cells have recently been published with mixed results.

Experimental and Clinical Regenerative Capability of Human Bone Marrow Cells After Myocardial Infarction

Francisco Fernández-Avilés, José Alberto San Román, Javier García-Frade, María Eugenia Fernández, María Jesús Peñarrubia, Luis de la Fuente, Manuel Gómez-Bueno, Alberto Cantalapiedra, Jesús Fernández, Oliver Gutierrez, Pedro L. Sánchez, Carolina Hernández, Ricardo Sanz, Javier García-Sancho, Ana Sánchez
Circulation Research. 2004;95:742-748

This study Showed that after implantation of BMCs No major cardiac events occurred up to 11±5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo.

Multipotent Progenitor Cells in Regenerative Cardiovascular Medicine.

Paediatric Cardiology Volume 30, Number 5 / July, 2009 pp 690-698

Abstract  Regenerative therapies for heart diseases require the understanding of the molecular mechanisms that govern the fates and differentiation of the diverse muscle and non-muscle cell lineages that form during heart development. During mouse cardiogenesis, the major lineages of the mature heart, cardiomyocytes, smooth muscle, endothelial cells, and cardiac mesenchyme, arise from multipotent cardiovascular progenitors expressing the transcription factors Mesp1, Isl1, Nkx2-5, and Tbx18. Recent identification of stem/progenitor cells of embryonic origin with intrinsic competence to differentiate into multiple lineages of the heart offers exciting new possibilities for cardiac regeneration. When combined with new advances in nuclear reprogramming, the prospect of achieving autologous, cardiomyogenic, stem-cell-based therapy might be within reach.

Cardiogenesis and the Complex Biology of Regenerative Cardiovascular Medicine

Kenneth R. Chien,1,2* Ibrahim J. Domian,1 Kevin Kit Parker3

Abstract: The heart is a complex organ system composed of a highly diverse set of muscle and non-muscle cells. Understanding the pathways that drive the formation, migration, and assembly of these cells into the heart muscle tissue, the pacemaker and conduction system, and the coronary vasculature is a central problem in developmental biology. Efforts to unravel the biological complexity of in vivo cardiogenesis have identified a family of closely related multipotent cardiac progenitor cells. These progenitors must respond to non–cell-autonomous signalling cues to expand, differentiate, and ultimately integrate into the three-dimensional heart structures. Coupling tissue-engineering technologies with patient-specific cardiac progenitor biology holds great promise for the development of human cell models of human disease and may lay the foundation for novel approaches in regenerative cardiovascular medicine.

Genetic Proof-of-Concept for Cardiac Gene Expression in Human Circulating Blood-Derived Progenitor Cells

Stefan Rupp, MD, Masamichi Koyanagi, MD, Masayoshi Iwasaki, MD, Florian Diehl, PhD, Philipp Bushoven, Dietmar Schranz, MD, Andreas M. Zeiher, MD and Stefanie Dimmeler, PhD*

To the Editor: Transplantation of adult bone marrow– or blood-derived autologous progenitor cells is a promising option for treatment of patients with acute myocardial infarction or heart failure. Initial randomised, double-blind clinical trials demonstrated encouraging results suggesting that cell therapy improves heart function and patients' prognosis (1,2). However, the mechanisms underlying the beneficial effects of cell therapy are discussed controversially.

In summary, these experiments provide indisputable genetic evidence that circulating progenitor cells can be induced to express cardiac-specific genes. Although the number of cells acquiring a cardiac phenotype is rather low, the proof-of-concept that cardiac gene expression can be induced opens the possibility of enhancing cardiac differentiation capacity and thereby increasing the regenerative potential of circulating progenitor cells.

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