Myocardial oxygenation and functional recovery in infarct rat hearts transplanted with mesenchymal stem cells

• Published in: American journal of physiology. Heart and circulatory physiology 2009-05, Vol.296 (5), p.H1263-H1273
• Main Authors: Chacko, Simi M, Khan, Mahmood, Kuppusamy, M. Lakshmi, Pandian, Ramasamy P, Varadharaj, Saradhadevi, Selvendiran, Karuppaiyah, Bratasz, Anna, Rivera, Brian K, Kuppusamy, Periannan
• Format: Article
• Language: English
• Subjects: Animals; Cell Differentiation; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Echocardiography; Electron Spin Resonance Spectroscopy; Endocytosis; Fibrosis; Heart; Heart attacks; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells - metabolism; Molecular Probes - metabolism; Molecular Probes - toxicity; Myocardial Contraction; Myocardial Infarction - metabolism; Myocardial Infarction - physiopathology; Myocardial Infarction - surgery; Myocardium - metabolism; Myocardium - pathology; Neovascularization, Physiologic; Oximetry - methods; Oxygen; Oxygen - metabolism; Oxygen Consumption; Rats; Rats, Inbred F344; Recovery of Function; Regeneration; Rodents; Stem cells; Stroke Volume; Time Factors; Tissues; Transplantation, Homologous; Ventricular Function, Left
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01311.2008

Division of Cardiovascular Medicine, Department of Internal Medicine, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio Submitted 18 December 2008 ; accepted in final form 5 March 2009 Stem cell therapy for myocardial tissue repair is limited by the poor survival of transplanted cells, possibly because of inadequate supply of oxygen and nutrients. The purpose of this study was to assess the oxygenation level and functional recovery after allogenic transplantation of mesenchymal stem cells (MSC) in a rat model of myocardial infarction (MI). Myocardial oxygen tension (P O 2 ) was measured by electron paramagnetic resonance oximetry using an implantable oxygen-sensing spin probe (OxySpin). MSCs incubated with OxySpins showed substantial uptake of the probe without affecting its oxygen sensitivity or calibration. The cells internalized with OxySpins were able to differentiate into osteogenic, adipogenic, cardiomyocyte, and endothelial cell lineages. The labeled cells tested positive for CD44 and CD29 markers and negative for the hematopoietic markers CD14 and CD45. For the in vivo studies, MI was induced in rats by permanently ligating the left anterior descending coronary artery. MSCs with OxySpins were transplanted in the infarct region of hearts. A significant increase in P O 2 was observed in the MSC group compared with the untreated MI group (18.1 ± 2.6 vs. 13.0 ± 1.8 mmHg, n = 4, P < 0.05) at 4 wk after transplantation. Echocardiography showed a significant improvement in ejection fraction and fraction shortening, which inversely correlated with the magnitude of fibrosis in the treated hearts. The cell-transplanted hearts also showed an increase in vascular endothelial growth factor level and capillary density in the infarct region. The study established our ability to measure and correlate changes in myocardial tissue oxygenation with cardiac function in infarcted rat hearts treated with MSCs. myocardial infarction; oxygen-sensing spin probe; electron paramagnetic resonance oximetry Address for reprint requests and other correspondence: P. Kuppusamy, Davis Heart and Lung Research Institute, The Ohio State Univ., 420 W. 12th Ave, Rm. 114, Columbus, OH 43210 (e-mail: kuppusamy.1{at}osu.edu )