Circulation. 2003;107:1322-1328
Published online before print February 17, 2003, doi: 10.1161/01.CIR.0000055313.77510.22
Published online before print February 17, 2003, doi: 10.1161/01.CIR.0000055313.77510.22
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(Circulation. 2003;107:1322.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Stromal Cell–Derived Factor-1 Effects on Ex Vivo Expanded Endothelial Progenitor Cell Recruitment for Ischemic Neovascularization
From the Division of Cardiovascular Research and Medicine (J.Y., K.F.K., O.M., A.K., M.S., S.M., M.B.M., D.W.L., J.M.I., T.A.), St Elizabeth’s Medical Center, Tufts University School of Medicine, Boston, Mass, and Department of Physiology (H.M., T.A.), Tokai University School of Medicine, Tokai, Japan.
Correspondence to Takayuki Asahara, MD, PhD, or Douglas W. Losordo, MD, Division of Cardiovascular Research and Medicine, St Elizabeth’s Medical Center, 736 Cambridge St, Boston, MA, 02135. E-mail asa777{at}aol.com (T.A.) or douglas.losordo@tufts.edu
Background— Stromal cell–derived factor-1 (SDF-1) is a chemokine considered to play an important role in the trafficking of hematopoietic stem cells. Given the close relationship between hematopoietic stem cells and endothelial progenitor cells (EPCs), we investigated the effect of SDF-1 on EPC-mediated vasculogenesis.
Methods and Results— Flow cytometric analysis demonstrated expression of CXCR4, the receptor of SDF-1, by 66±3% of EPCs after 7 days in culture. In vitro modified Boyden chamber assay showed a dose-dependent EPC migration toward SDF-1 (control versus 10 ng/mL SDF-1 versus 100 ng/mL SDF-1, 24±2 versus 71±3 versus 140±6 cells/mm2; P<0.0001). SDF-1 attenuated EPC apoptosis (control versus SDF-1, 27±1 versus 7±1%; P<0.0001). To investigate the effect of SDF-1 in vivo, we locally injected SDF-1 into athymic ischemic hindlimb muscle of nude mice combined with human EPC transplantation to determine whether SDF-1 augmented EPC-induced vasculogenesis. Fluorescence microscopic examination disclosed increased local accumulation of fluorescence-labeled EPCs in ischemic muscle in the SDF-1 treatment group (control versus SDF-1=241±25 versus 445±24 cells/mm2, P<0.0001). At day 28 after treatment, ischemic tissue perfusion was improved in the SDF-1 group and capillary density was also increased. (control versus SDF-1, 355±26 versus 551±30 cells/mm2; P<0.0001).
Conclusion— These findings indicate that locally delivered SDF-1 augments vasculogenesis and subsequently contributes to ischemic neovascularization in vivo by augmenting EPC recruitment in ischemic tissues.
Key Words: chemokines • angiogenesis • ischemia • endothelium
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