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This Article Full Text Full Text (PDF) All Versions of this Article: 293/4/H2129    most recent 00677.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Khan, M. Articles by Kuppusamy, P. Search for Related Content PubMed PubMed Citation Articles by Khan, M. Articles by Kuppusamy, P.

Skeletal myoblasts transplanted in the ischemic myocardium enhance in situ oxygenation and recovery of contractile function

¹Center for Biomedical Electron Paramagnetic Resonance Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine; ²Division of Cardiothoracic Surgery, Department of Surgery; The Ohio State University, Columbus, Ohio

Submitted 11 June 2007 ; accepted in final form 24 July 2007

It is unclear whether oxygen plays a role in stem cell therapy. Hence, the determination of local oxygenation (PO₂) in the infarct heart and at the site of transplantation may be critical to study the efficacy of cell therapy. To demonstrate this, we have developed an oxygen-sensing paramagnetic spin probes (OxySpin) to monitor oxygenation in the region of cell transplantation using electron paramagnetic resonance (EPR) spectroscopy. Skeletal myoblast (SM) cells isolated from thigh muscle biopsies of mice were labeled with OxySpin by coculturing the cells with submicron-sized (270 ± 120 nm) particulates of the probe. Myocardial infarction was created by left coronary artery ligation in mice. Immediately after ligation, labeled SM cells were transplanted in the ischemic region of the heart. The engraftment of the transplanted cells and in situ PO₂ in the heart were monitored weekly for 4 wk. EPR measurements revealed the retention of cells in the infarcted tissue. The myocardial PO₂ at the site of SM cell therapy was significantly higher compared with the untreated group throughout the 4-wk period. Histological studies revealed differentiation and engraftment of SM cells into myotubes and increased incidence of neovascularization in the infarct region. The infarct size in the treated group was significantly decreased, whereas echocardiography showed an overall improvement in cardiac function when compared with untreated hearts. To our knowledge, this the first report detailing changes in in situ oxygenation in cell therapy. The increased myocardial PO₂ positively correlated with neoangiogenesis and cardiac function.

ischemic heart; myocardial infarction; electron paramagnetic resonance oximetry; OxySpin