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| AATS/NHLBI: Cardiothoracic Surgery Exploring Collaborative Clinical Research Opportunities |
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Title and Author Adult Human Stem Cells in Cardiovascular Disease Repair/RegenerationJames T. Willerson, M.D. Abstract Recent studies have shown that bone marrow and adipose tissue-derived human adult stem cells, when healthy, and injected into a coronary artery or directly into the heart in patients with CAD and ischemic cardiomyopathies, improve coronary blood flow and ventricular function. Specific types of adult human stem cells, such as pre-mesenchymal and mesenchymal stem cells, stem cells expressing aldehyde dehydrogenese, and CD34+ stem cells improve coronary blood flow and consequently, ventricular function in patients with ischemic cardiomyopathies and peripheral blood flow to ischemic limbs. The improvement in ventricular function in patients and experimental animal models seen with these cells appears to be predominately due to increased coronary blood flow.Mesenchymal and pre-mesenchymal stem cells appear to not be rejected when given to different individuals. This may prove to be a great advantage in treating future patients whose own cardiac stem cells are dysfunctional. In SCID mice (immunologically incompetent mice) with experimentally �created MIs, human adult CD34+ stem cells injected into the tail veins or directly into the LV cavities fuse their nuclei with those of reversibly injured murine nuclei turning on the cell cycle and generating new cardiac myocytes, albeit at a relatively low level of activity. The receptors for the nuclear fusion are VCAM and alpha4 beta1 receptors. The CD 34+ and adult human cells also differentiate into endothelial cells, smooth muscle cells, and some new cardiac myocytes. However, in some elderly patients with severe heart failure, the adult human cardiac stem cells are dysfunctional, i.e. they cannot reproduce themselves in culture. When these cells are injected into patients with ischemic cardiomyopathies, they do not improve the function of these hearts. Future opportunities to advance the field of adult human cardiac stem cells in repair and regeneration of the hearts of patients with ischemic (and perhaps non-ischemic) cardiomyopathies include:
Key Research Gap Requiring NHLBI Leadership The most pressing need is to further develop and evaluate iPS cells and fibroblasts and mesenchymal stem cells that have been transformed into cardiac myocytes in their ability to contribute to cardiovascular repair and regeneration. I believe that this is a development likely to impact the field greatly in the near future. Key Citations 1:2: 3: |
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Copyright © 2012 American Association for Thoracic Surgery
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
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It is very important that you consult a doctor about any specific medical problem or question.
All rights reserved. IMPORTANT REMINDER: The preceding information is intended only to provide
general guidance and not as a definitive basis for diagnosis or treatment in any particular case.
It is very important that you consult a doctor about any specific medical problem or question.