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Improved Cell Survival in Infarcted Myocardium Using a Novel Combination Transmyocardial Laser and Cell Delivery System

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Stem cell therapy has been used to treat ischemic cardiac disease with promising early results. However, there has been limited success using cell therapy in infarcted tissue. The cells have an inadequate microvascular environment in order to survive once implanted into scar tissue. The goal of this study was to create a microvascular environment into infarcted myocardial tissue using transmyocardial laser revascularization (TMR) as a pretreatment before cell implantation and evaluate cell survival afterwards. Balloon occlusion catheter-based myocardial infarct of the circumflex artery was created in a porcine model. The infarct was allowed to mature for 2 weeks. Three groups consisting of TMR alone (TMR), TMR + fluorescent-labeled allogeneic mesenchymal stem cells (MSCs) (TMR + Cells), and MSCs alone (Cells) were injected into the infarcted tissue using a combination TMR and cell delivery system (PhoenixTM, Cardiogenesis). The hearts were explanted at 1 week after treatment for cell and tissue evaluation. The myocardial infarcts were verified in all animals using both ultrasound and direct visual imaging. All arms of the study were successful with a mean of 2.0 ± 106 MSCs injected per site into the scar tissue. All animals survived to explant at 1 week. On histological examination, 300 high-power fields were evaluated demonstrating that the TMR + Cells group had 25 ± 5 cells and the Cells group 5 ± 2 cells compared to baseline TMR alone by fluorescence. The use of TMR as a pretreatment for MSC injection increases early cell survival in infarcted tissue without increased adverse events. Further long-term functional and differentiation analysis will be required to evaluate the efficacy for future clinical translation.

Keywords: Cell therapy; Heart; Mesenchymal stem cell; Porcine; Transmyocardial laser

Document Type: Research Article


Affiliations: 1: Center for Cardiac Cell Therapy-Heart Lung Esophageal Surgical Institute and Cardiovascular Institute, University of Pittsburgh/UPMC/McGowan Institute of Regenerative Medicine, Pittsburgh, PA, USA 2: Regenerative Bioscience Center, University of Georgia, Athens, GA, USA

Publication date: 2007-09-01

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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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