Skeletal myoblasts transplanted in the ischemic myocardium enhance in situ oxygenation and recovery of contractile function.
It is unclear whether oxygen plays a role in stem cell therapy. Hence, the determination of local oxygenation (Po(2)) 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 Po(2) in the heart were monitored weekly for 4 wk. EPR measurements revealed the retention of cells in the infarcted tissue. The myocardial Po(2) 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 Po(2) positively correlated with neoangiogenesis and cardiac function.
Center for Biomedical Electron Paramagnetic Resonance Spectroscopy and Imaging, Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Mahmood
M
Khan
Vijay Kumar
VK
Kutala
Deepti S
DS
Vikram
Sheik
S
Wisel
Simi M
SM
Chacko
M Lakshmi
ML
Kuppusamy
Iyyapu K
IK
Mohan
Jay L
JL
Zweier
Pawel
P
Kwiatkowski
Periannan
P
Kuppusamy
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005240:Feasibility Studies; D006614:Hindlimb; D008026:Ligation; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D018919:Neovascularization, Physiologic; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010313:Partial Pressure; D015203:Reproducibility of Results; D033581:Stem Cell Transplantation; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D010100:Oxygen