Gene expression profiles following intracoronary injection of mesenchymal stromal cells using a porcine model of chronic myocardial infarction |
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| Authors: | Barallobre-Barreiro Javier de Ilárduya Oskar Martínez Moscoso Isabel Calviño-Santos Ramón Aldama Guillermo Centeno Alberto López-Pelaez Eduardo Doménech Nieves |
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| Affiliation: | 1. Unidad de Investigación;2. Networking Center of Biomedical Research in Bioengineering, Biomaterials and Nanomedicine;3. Unidad de Hemodinámica;4. Centro de Experimentación, INIBIC-CHU A Coruña, A Coruña, Spain;1. MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA;2. Department of Physiology, Semmelweis University, Budapest 1085, Hungary;3. Department of Paediatrics, Paracelsus Medical University, SALK Salzburg, Salzburg 5020, Austria;4. Department of Pediatrics, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea;2. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea;3. Clinical Research Institute, Seoul National University Hospital, Seoul, Korea;4. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Lung Institute, Seoul National University College of Medicine, Seoul, Korea;5. Department of Internal Medicine, Seoul Municipal Boramae Hospital, Seoul, Korea;6. Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si, Korea;7. Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea;1. Department of Medicine V, Heidelberg University, Heidelberg, Germany;2. Department of Medical Biometry, Heidelberg University, Heidelberg, Germany;1. University Medical Center Hamburg-Eppendorf, Department of Transfusion Medicine, Hamburg, Germany;2. University Medical Center Hamburg-Eppendorf, Clinic for Stem Cell Transplantation, Hamburg, Germany;3. New York University School of Medicine, New York, New York, USA |
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| Abstract: | Background aimsWe evaluated the therapeutic potential of injection of in vitro differentiated bone marrow mesenchymal stromal cells (MSC) using a swine model.Methods and ResultsMyocardial infarction was induced by coronary occlusion. Three groups (n = 5 each) were analyzed: one group received an injection of 17.8 ± 9.3 × 106 5-azacytidine-treated allogeneic MSC 1 month after infarction; a placebo group received an injection of medium; and controls were kept untreated. After 4 weeks, heart samples were taken from three infarcted areas, interventricular septa, ventricles and atria. Gene expression profiles of genes related to contractility (Serca2a), fibrosis (Col1a1), cardiomyogenesis (Mef2c, Gata4 and Nkx2.5) and mobilization of stem cells (Sdf1, Cxcr4 and c-kit) were compared by quantitative real-time PCR (qRT-PCR). Gene expression profiles varied in different heart areas. Thus Serca2a expression was reduced in infarcted groups in all heart regions except for the left ventricles, where Col1a1 was overexpressed. The expression of genes related to cardiomyogenesis decreased in the infarcted zones and left atria compared with healthy hearts. Interestingly, increased expression of Cxcr4 was detected in infarcted regions of MSC-treated pigs compared with the placebo groupConclusionsInfarction induced changes in expression of genes involved in various biologic processes. Genes involved in cardiomyogenesis were downregulated in the left atrium. The intracoronary injection of MSC resulted in localized changes in the expression of Cxcr4. |
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