Avemar and Echinacea extracts enhance mobilization and homing of CD34+ stem cells in rats with acute myocardial infarction

Abstract

Introduction: Activation of endogenous stem cell mobilization can contribute to myocardial regeneration after ischemic injury. This study aimed to evaluate the possible role of Avemar or Echinacea extracts in inducing mobilization and homing of CD34+ stem cells in relation to the inflammatory and hematopoietic cytokines in rats suffering from acute myocardial infarction (AMI). Methods: AMI was developed by two consecutive subcutaneous injections of isoprenaline (85 mg/kg). AMI rats were either post-treated or pre- and post-treated daily with oral doses of Avemar (121 mg/kg) or Echinacea (130 mg/kg). In whole blood, the number of CD34+ cells was measured by flow cytometry and their homing to the myocardium was immunohistochemically assessed. Serum creatine kinase, vascular endothelial growth factor, interleukin-8 and granulocyte macrophage colony stimulating factor were determined on days 1, 7 and 14 after AMI. Sections of the myocardium were histopathologically assessed. Results: Rats pre- and post-treated with Avemar or Echinacea exhibited substantial increases in the number of circulating CD34+ cells, peaking on the first day after AMI to approximately 13-fold and 15-fold, respectively, with a decline in their level on day 7 followed by a significant increase on day 14 compared to their corresponding AMI levels. Only post-treatment with Echinacea caused a time-dependent increase in circulating CD34+ cells on days 7 and 14. Such increases in circulating CD34+ cells were accompanied by increased homing to myocardial tissue 14 days after AMI. Interestingly, pre- and post-treatment with Avemar or Echinacea substantially increased serum creatine kinase on day 1, normalized its activity on day 7 and, on continued treatment, only Echinacea markedly increased its activity on day 14 compared to the corresponding AMI values. Moreover, both treatments modified differently the elevated serum vascular endothelial growth factor and the lowered granulocyte macrophage colony stimulating factor levels of the AMI group but did not affect the level of interleukin-8. These results were supported histopathologically by reduced inflammatory reactions and enhanced neovascularization. Conclusion: Avemar and Echinacea extracts can effectively induce mobilization and homing of CD34+ stem cells to the myocardial tissue and thus may help in stem cell-based regeneration of the infarcted myocardium.