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

Mahmood Khan, Vijay Kumar Kutala, Deepti S. Vikram, Sheik Wisel, Simi M. Chacko, M. Lakshmi Kuppusamy, Iyyapu K. Mohan, Jay L. Zweier, Pawel Kwiatkowski, Periannan Kuppusamy

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 2007
Externally publishedYes

Keywords

  • Electron paramagnetic resonance oximetry
  • Ischemic heart
  • Myocardial infarction
  • OxySpin

ASJC Scopus subject areas

  • Physiology

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