Differences in donor CXCR4 expression levels are correlated with functional capacity and therapeutic outcome of angiogenic treatment with endothelial colony forming cells
| Autor: | Kwang Won Kim, Bae Jun Oh, Deog Kyeom Kim, Kang Sup Yoon, Byoung Jae Kim, Myung-Shik Lee, Jae Hyeon Kim, Sang Gyu Park, Kyong Soo Park |
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| Rok vydání: | 2010 |
| Předmět: |
Male
MAPK/ERK pathway Benzylamines Receptors CXCR4 Nitric Oxide Synthase Type III Myocardial Ischemia Biophysics Mice Nude Neovascularization Physiologic Cyclams Biochemistry CXCR4 Umbilical Cord Andrology Neovascularization Mice Phosphatidylinositol 3-Kinases Cell Movement Heterocyclic Compounds In vivo Enos Living Donors medicine Animals Humans Phosphorylation Progenitor cell Molecular Biology Protein kinase B Cells Cultured biology Stem Cells Cell migration Cell Biology biology.organism_classification Chemokine CXCL12 Immunology Endothelium Vascular medicine.symptom Proto-Oncogene Proteins c-akt Stem Cell Transplantation |
| Zdroj: | Biochemical and Biophysical Research Communications. 398:627-633 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2010.06.108 |
| Popis: | 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-1alpha-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-1alpha-induced migratory capacity. ECFCs with high CXCR4 expression showed enhanced ERK and Akt activation in response to SDF-1alpha. In addition, SDF-1alpha-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. |
| Databáze: | OpenAIRE |
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