SDF-1 Recruits Cardiac Stem Cell-Like Cells That Depolarize In Vivo

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Abstract:

Prolongation or reestablishment of stem cell homing through the expression of SDF-1 in the myocardium has been shown to lead to homing of endothelial progenitor cells to the infarct zone with a subsequent increase in vascular density and cardiac function. While the increase in vascular density is important, there could clearly be other mechanisms involved. In a recent study we demonstrated that the infusion of mesenchymal stem cells (MSC) and MSC that were engineered to overexpress SDF-1 led to significant decreases in cardiac myocyte apoptosis and increases in vascular density and cardiac function compared to control. In that study there was no evidence of cardiac regeneration from either endogenous stem cells or the infused mesenchymal stem cells. In this study we performed further detailed immunohistochemistry on these tissues and demonstrate that the overexpression of SDF-1 in the newly infracted myocardium led to recruitment of small cardiac myosin-expressing cells that had proliferated within 2 weeks of acute MI. These cells did not differentiate into mature cardiac myocytes, at least by 5 weeks after acute MI. However, based on optical mapping studies, these cells appear capable of depolarizing. We observed greater optical action potential amplitude in the infarct border in those animals that received SDF-1 overexpressing MSC than observed in noninfarcted animals and those that received control MSC. Further immunohistochemistry revealed that these proliferated cardiac myosin-positive cells did not express connexin 43, but did express connexin 45. In summary, our study suggests that the prolongation of SDF-1 expression at the time of acute MI leads to the recruitment of endogenous cardiac myosin stem cells that may represent cardiac stem cells. These cells are capable of depolarizing and thus may contribute to increased contractile function even in the absence of maturation into a mature cardiac myocyte.

Keywords: Cardiac myocytes; Cardiac stem cells; Depolarization; SDF-1 expression

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368907783338271

Affiliations: 1: Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH, USA 2: †Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH, USA 3: Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH, USA 4: Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, OH, USA

Publication date: September 1, 2007

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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