Rationale: Vascular progenitor cells play crucial roles in physiological and pathological vascular remodelinga process that is crucial for the regeneration of acellular biodegradable scaffolds engineered as vital strategies against the limited availability of healthy autologous vessels for bypass grafting. unknown. Methods and Results: Vascular stem/progenitor cells were isolated from murine aortic adventitia and selected for the Sca-1 (stem cell antigen-1) marker. Dkk3 induced the chemotaxis of Sca-1+ cells in vitro in transwell and wound healing assays and former mate vivo in the aortic band assay. Functional research to recognize Dkk3 receptor uncovered that overexpression or knockdown of chemokine receptor CXCR7 (C-X-C chemokine receptor type 7) in Sca-1+ cells led to modifications in cell migration. Coimmunoprecipitation tests using Sca-1+ cell ingredients treated with Dkk3 demonstrated the physical relationship between CXCR7 and DKK3, and particular saturation binding assays determined a high-affinity Dkk3-CXCR7 binding using a dissociation continuous of 14.14 nmol/L. Binding of CXCR7 by Dkk3 brought about the next activation of ERK1/2 (extracellular signal-regulated kinases 1/2)-, PI3K (phosphatidylinositol 3-kinase)/AKT (proteins kinase B)-, Rac1 (Ras-related C3 botulinum toxin substrate 1)-, and RhoA (Ras homolog gene family members, member A)-signaling pathways involved with Sca-1+ cell migration. Tissue-engineered vessel grafts had been fabricated with or without 7-Methylguanine Dkk3 and implanted to displace the rat abdominal aorta. Dkk3-packed tissue-engineered vessel grafts demonstrated effective recruitment and endothelization of vascular progenitor cells, which had obtained characteristics of older smooth muscle tissue cells. CXCR7 preventing using particular antibodies within this vessel graft model hampered stem/progenitor cell recruitment in to the vessel wall structure, compromising vascular remodeling thus. Conclusions: We offer a book and solid proof that CXCR7 acts as Dkk3 receptor, which mediates Dkk3-induced vascular progenitor migration in vitro and in tissue-engineered vessels, harnessing patent grafts resembling indigenous arteries hence. check). E, American blot 7-Methylguanine evaluation of CXCR7 knockdown in Sca-1+ cells transfected with CXCR7 siRNA. H and F, Representative pictures of transwell migration assay of Sca-1+ cells transfected with CXCR7 siRNA in response to Dkk3 (25 ng/mL) and Sdf-1 (stromal cell-derived aspect 1; 25 ng/mL) treatment, respectively. G and I, Quantitative evaluation from the migrated cells in response to Dkk3 or Sdf-1 treatment (n=4; 2-method ANOVA accompanied by Bonferroni check). CXCR7 knockdown in Sca-1-VPCs supresses Dkk3-mediated migration, towards the observed with Sdf-1 treatment similarly. The info are portrayed as the meanSEM of three to five 5 independent tests. NS indicates non-significant. **check). D, American blot evaluation of CXCR7 overexpression in HEK 293T cells transfected with CXCR7 appearance plasmid. F and E, Consultant Hepacam2 binding curves and particular Scatchard evaluation of Sdf-1 (stromal cell-derived aspect 1)Calkaline phosphatase (AP) binding to CXCR4 or CXCR7 overexpressed in HEK 293T cells and of Dkk3-AP binding to CXCR7, 7-Methylguanine CXCR4, Kremen1, or Kremen2 overexpressed in HEK 293T cells, respectively. The dissociation constants are symbolized for every receptor (n=3). Dkk3-AP will not bind to CXCR4, 7-Methylguanine Kremen1, and Kremen2, but it does bind with high affinity to CXCR7, as represented by the characteristic hyperbolic binding curve. CXCR7 is also a high-affinity binding receptor of Sdf-1, alongside its cognate receptor CXCR4. AP 7-Methylguanine alone does not bind to CXCR7, as depicted in blue. G and I, Representative images of transwell migration assay of HEK 293T cells overexpressing CXCR7 in response to Dkk3 and Sdf-1 activation, respectively. H and J, Quantitative analysis of the transwell migration assays. Dkk3 induces migration of CXCR7-overexpressing HEK 293T cells, analogously to Sdf-1. (n=5; 2-way ANOVA followed by Bonferroni post hoc test). The data are expressed as the meanSEM of 3 to 5 5 independent experiments. *was 13.26 days. *These authors contributed equally to this article. The online-only Data Product is available with this short article at https://www.ahajournals.org/doi/suppl/10.1161/CIRCRESAHA.118.312945. Novelty and Significance What Is Known? Dkk3 (dickkopf-3) is usually involved in vascular remodeling, for example, atherosclerosis, vascular injury-induced stenosis, and plaque stability. Tissue-engineered vessel grafts constitute an effective alternative to the limited availability of autografts utilized for blood vessel replacement. Vascular progenitor cells play an active role in vascular remodeling and regeneration. What New Information Does THIS SHORT ARTICLE Contribute? Dkk3 can specifically bind to a chemokine receptor CXCR7 (C-X-C.