Differential effect of ischaemic preconditioning on mobilisation and recruitment of haematopoietic and mesenchymal stem cells in porcine myocardial ischaemia-reperfusion

Thromb Haemost. 2010 Aug;104(2):376-84. doi: 10.1160/TH09-08-0558. Epub 2010 Mar 29.

Abstract

Effects of ischaemic preconditioning (IP) on the mobilisation and recruitment of haematopoietic (HSCs) and mesenchymal stem (MSC) cells were determined in porcine coronary occlusion/reperfusion. Thirty-three pigs underwent percutaneous occlusion of the left anterior descending coronary artery (LAD) for 90 minutes (min), followed by 120 min reperfusion. IP was performed in 16 of the 33 pigs by two cycles of 5 min balloon occlusion/reperfusion prior to the 90 min occlusion (group IP vs. group C). Peripheral blood and myocardial tissue concentration of bone marrow origin HSCs (characterised by coexpression of CD31+, CD90+, CD45+) and MSCs (characterised by coexpression of CD44+, CD90+, CD45-) were measured by flow cytometry in the early phase of IP. Plasma/serum levels of stem cell mobilisation factors (stromal cell-derived factor-1a [SDF-1a], vascular endothelial growth factor [VEGF], tumour necrosis factor a[TNF-a] and interleukin-8 [IL-8]) were measured. IP led to a significant increase in circulating HSCs as compared with the group C (475 +/- 233 vs. 281 +/- 264 /ml, p=0.032) in the early phase of IP. In contrast, a rapid and prolonged decrease in level of circulating MSCs was observed in group IP as compared with group C (19 +/- 12 vs. 32 +/- 17 /ml, p=0.015). The recruitment of HSCs and MSCs in infarct and border zone was significantly greater in IP group, indicating a faster homing of MSCs as compared with the rate of mobilisation. Rapid increase in VEGF, TNF-a and IL-8 levels was induced by IP, which, however, was not correlated with the levels of circulating SCs. In conclusion, IP resulted in differential mobilisation and recruitment of HSCs and MSCs in the early phase of cardioprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Chemokine CXCL12 / blood
  • Chemotaxis*
  • Disease Models, Animal
  • Flow Cytometry
  • Hematopoietic Stem Cells / immunology
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Hyaluronan Receptors / analysis
  • Interleukin-8 / blood
  • Ischemic Preconditioning, Myocardial*
  • Leukocyte Common Antigens / analysis
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Myocardial Infarction / blood
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / analysis
  • Sus scrofa
  • Thy-1 Antigens / analysis
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Endothelial Growth Factor A / blood
  • Ventricular Function, Left

Substances

  • Chemokine CXCL12
  • Hyaluronan Receptors
  • Interleukin-8
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Thy-1 Antigens
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Leukocyte Common Antigens