P4.12 EGRESS OF FUNCTIONALLY COMPETENT PROGENITOR CELLS OVER-EXPRESSING CXCR4 FROM THE BONE MARROW FOLLOWING CARDIAC SURGERY WITH THE USE OF CARDIOPULMONARY BYPASS

Abstract

Background: The mechanisms of endogenous progenitor cell trafficking in response to tissue injury in humans are poorly understood. Methods: We based our study on a model of transient myocardial injury, provoked by the use of cardiopulmonary bypass during cardiac surgery in 39 patients. Bone marrow (BM) and blood samples were collected at baseline and after disconnection of bypass machine. CD34+/CD133+ cell numbers (% of 100000 lymphocytes) and stem cell trafficking molecule CXC-chemokine receptor 4 (CXCR4) expression on CD34+ cells were measured by flow cytometry. Hematopoietic colony formation units (CFU) and stromal cell-derived factor-1 alpha dependent chemotaxis were also analyzed. Results: Increased numbers of circulating progenitor cells after surgery (1.64±0.18% vs 1.02±0.17%, p=0.003) directly correlated with baseline BM (r=0.7, p<0.0001) and inversely - with post-bypass BM counts (r= −0.9, p=0.008), indicating that circulating cells were mobilized from BM. Following surgery expression of CXCR4 on circulating progenitors increased (88±43 vs 113±72 mean fluorescence intensity (MFI), p=0.031). In post-bypass BM samples CXCR4 expression on CD34+ cells decreased (58±22 MFI vs 44±15 MFI, p=0.03), suggesting that over-expressing CXCR4 cells, being the most suitable for non-marrow tissues migration, were released into circulation. Positive relationship between magnitude of CXCR4 expression on mobilized progenitors and cardiopulmonary bypass time (r=0.7, p=0.015) were shown. Progenitors in post-bypass blood samples compared to baseline had increased chemotactic (46±16% vs 59±22%, p=0.002) and clonogenic (70±25 vs 110±70 CFUs) potential. Conclusion: Increased expression of CXCR4 on mobilised functionally competent progenitors suggests about their ability to migrate towards non-marrow tissues, such as ischemic myocardium.