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Differences in donor CXCR4 expression levels are correlated with functional capacity and therapeutic outcome of angiogenic treatment with endothelial colony forming cells

Cited 32 time in Web of Science Cited 31 time in Scopus
Authors
Oh, Bae Jun; Kim, Deog Kyeom; Kim, Byoung Jae; Yoon, Kang-Sup; Park, Kyong Soo; Kim, Kwang-Won; Kim, Jae Hyeon; Lee, Myung-Shik; Park, Sang Gyu
Issue Date
2010-08-06
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS; Vol.398 4; 627-633
Keywords
CXCR4Endothelial colony forming cellsSDF-1αNeovascularizationMigration
Abstract
CXCR4 expression is important for cell migration and recruitment, suggesting that the expression levels of CXCR4 may be correlated with functional activity of implanted cells for therapeutic neovascularization. Here, we examined differences between umbilical cord blood (CB) donors in the CXCR4 levels of endothelial colony forming cells (ECFCs), which are a subtype of endothelial progenitor cells (EPCs). We investigated the relationships between CXCR4 expression level and SDF-1 alpha-induced vascular properties in vitro, and their in vivo contributions to neovascularization. We found that ECFCs isolated from different donors showed differences in CXCR4 expression that were linearly correlated with SDF-1 alpha-induced migratory capacity. ECFCs with high CXCR4 expression showed enhanced ERK and Akt activation in response to SDF-1 alpha In addition, SDF-1 alpha-induced migration and ERK1/2, Akt, and eNOS activation were reduced by AMD3100, a CXCR4-specific peptide antagonist, or by SiRNA-CXCR4. Administration of high-CXCR4-expressing ECFCs resulted in a significant increase in therapeutic potential for blood flow recovery, tissue healing and capillary density compared to low-CXCR4-expressing ECFCs in hindlimb ischemia. Taken together, the functional differences among ECFCs derived from different donors depended on the level of CXCR4 expression, suggesting that CXCR4 expression levels in ECFCs could be a predictive marker for success of ECFC-based angiogenic therapy. (c) 2010 Elsevier Inc. All rights reserved.
ISSN
0006-291X
Language
English
URI
https://hdl.handle.net/10371/76459
DOI
https://doi.org/10.1016/j.bbrc.2010.06.108
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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