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(Circulation. 2006;114:186 – 192.)
© 2006 American Heart Association, Inc.

Cell Transplantation and Tissue Engineering

Role of Stromal-Derived Factor-1 in the Induction of Circulating CD34+CXCR4+ Progenitor Cells After Cardiac Surgery

Shigetoshi Mieno, MD; Basel Ramlawi, MD; Munir Boodhwani, MD; Richard T. Clements, PhD; Keisuke Minamimura, MD; Takashi Maki, MD; Shu-Hua Xu, PhD; Cesario Bianchi, MD, PhD; Jian Li, MD, PhD; Frank W. Sellke, MD

From the Division of Cardiothoracic Surgery (S.M., B.R., M.B., R.T.C., S.-H.X., C.B., J.L., F.W.S.) and Transplantation (K.M., T.M.), Beth Israel Deaconess Medical Center, Boston, Mass.

Correspondence to Frank W. Sellke, Division of Cardiothoracic Surgery, Harvard Medical School, Beth Israel Deaconess Medical Center, 110 Francis Street, Suite 2A, Boston, MA 02215. E-mail: fsellke{at}bidmc.harvard.edu

Background— Cardioplegia and cardiopulmonary bypass (CP/CPB) leads to an increase in circulating progenitor cells. The role of stromal-derived factor-1 (SDF-1), a key regulator of progenitor cell mobilization, and other cytokines in this process is not clear.

Methods and Results— Peripheral blood (n=24), atrial and skeletal tissue (n=6) samples were taken from patients undergoing CP/CPB before (pre-CP/CPB), 4 hours (post-CP/CPB), and 4 days (POD4) after CP/CPB. The number of circulating CD34+CXCR4+ cells increased post-CP/CPB (442±53 versus 286±27; P=0.04 versus pre-CP/CPB), but not at POD4 (382±50; P=0.28 versus pre-CP/CPB). Plasma levels of SDF-1 increased post-CP/CPB as compared with pre-CP/CPB (3325±325 versus 2911±165 pg/mL; P=0.046) but returned to baseline at POD4 (2838±224 pg/mL; P=0.90). Plasma levels of vascular endothelial growth factor were similar post-CP/CPB (P=0.90 versus pre-CP/CPB) but increased at POD4 (220±40 pg/mL versus 134±26 pg/mL; P=0.04 versus pre-CP/CPB). Serum levels of granulocyte-colony stimulating factor (G-CSF) increased early after CP/CPB as compared with pre-CP/CPB (265.0±41.7 versus 11.1±1.1 pg/mL; P<0.001) and returned to baseline at POD4 (P=0.84 versus pre-CP/CPB). The circulating CD34+CXCR4+ cells were positively correlated with plasma levels of SDF-1 early after CP/CPB (r=0.56, P<0.01), but not at other times. Protein expression of SDF-1 was elevated in the atrial myocardium after CP/CPB (9.4-fold; P=0.03).

Conclusions— Exposure to CP/CPB leads to an increase in circulating CD34+CXCR4+ progenitor cells, which is associated with increased myocardial SDF-1 expression. The numbers of CD34+CXCR4+ progenitor cells positively correlate with the plasma levels of SDF-1 post-CP/CPB, suggesting an important role of SDF-1 in progenitor cell mobilization.

Key Words: cardiac surgery • cardioplegia • cardiopulmonary bypass • cytokines • reperfusion • stem cells • stromal-derived factor

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