Submitted on June 11, 2007
Accepted on July 24, 2007
Skeletal Myoblasts Transplanted in the Ischemic Myocardium Enhance In Situ Oxygenation and Recovery of Contractile Function
Mahmood Khan1, Vijay Kumar Kutala1, Deepti S Vikram1, Sheik Wisel2, Simi M Chacko1, M. Lakshmi Kuppusamy1, Iyyapu K Mohan1, Jay L Zweier3, Pawel Kwiatkowski2, and Periannan Kuppusamy1*
1 Internal Medicine, The Ohio State University, Columbus, Ohio, United States
2 Surgery, The Ohio State University, Columbus, Ohio, United States
3 United States; Internal Medicine, The Ohio State University, Columbus, Ohio, United States
* To whom correspondence should be addressed. E-mail: kuppusamy.1{at}osu.edu.
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 co-culturing 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 four weeks. 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-week 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 while echocardiography showed an overall improvement in cardiac function when compared to 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.
