Coronary effluent from postconditioned hearts promotes survival of mesenchymal stem cells under hypoxia

Abstract

Objectives. Mesenchymal stem cells are sensitive to hypoxia under myocardial micro-environment of ischemia and reperfusion. Ischemic postconditioning, which is cardioprotective against ischemia–reperfusion injury, enhances in-vivo survival and therapeutic effects of transplanted stem cells. In this study, we investigated the effects of coronary effluent from postconditioned rat hearts on proliferation and survival of mesenchymal stem cells in vitro under hypoxia. Design. Isolated perfused rat hearts were divided into three groups (n = 6): the Sham group—receiving a 90 min perfusion; the Control group—receiving a 30 min global ischemia followed by a 60 min reperfusion; the ischemic postconditioning group—before sustained reperfusion, 3 cycles of 30 s reperfusion and 30 s ischemia were performed. Inflammation-related factors in coronary effluent were assessed by ELISA. Mesenchymal stem cells from bone marrow of Sprague–Dawley rats were cultured with coronary effluent under hypoxia (95% nitrogen, 5% carbon dioxide, and < 1% oxygen) for 6- or 18 h. Cell proliferation was determined by methyl thiazolyl tetrazolium. Survival rate was measured by Annexin V/PI. Results. Compared with ischemia–reperfusion treatment alone, postconditioning treatment increased the level of interleukin-10 and decreased the level of tumor necrosis factor-α and interleukin-1β in coronary effluent (P < 0.01). Stem cells cultured with postconditioned effluent, compared with those with ischemia–reperfusion effluent, had a higher proliferation (optical density value), more surviving cells, and less necrosis (P < 0.01). Conclusions. Coronary effluent from postconditioned hearts may promote the proliferation and survival of mesenchymal stem cells under hypoxia, and the suppression of inflammation may be involved in this process.

Key words::

• hypoxia
• ischemic postconditioning
• mesenchymal stem cells
• proliferation
• survival

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported in part by the National Natural Science Foundation of China (81100151; 81170196), the Science Foundation for Distinguished Young Scholars of Fujian Province, China (2013J06015), the Science and Technology Project of Education Department of Fujian Province, China (JA12132), and the Youth Foundation of Health Department of Fujian Province, China (2009-1-18).