Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation

Tan, Wenbin; Wang, J.; Zhou, Fang; Gao, Liuchun; Yin, Rong; Liu, H.; Sukanthanag, A.; Wang, G.; Mihm, Martín C.; Chen, D.‐B.; Nelson, J. Stuart

doi:10.1111/bjd.15716

Cited by 41 publications

(69 citation statements)

References 47 publications

(56 reference statements)

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“…Human dermal microvascular endothelial cells (hDMVECs) were cultured in endothelial cell basal medium (ECBM) with growth supplement (Cell Applications, Inc.) as previously described. 12 In order to establish the EC models with coexpression of EphB1 receptors and ephrin-B2 ligands, which mimic the pathological phenotypes of PWS ECs, we isolated a subset of normal hDMVECs with high expression of surface EphB1 receptors via biotinylated chimera ephrin-B2-Fc, which contains the extracellular portion of ephrin-B2 ligands and is capable of binding to EphB1 receptors, and streptavidin-conjugated magnetic beads. The rationale of this selection is that the ephrin-B2-Fc chimera ligand binds to EphB1 þ ∕EphB4 þ expressing venous and capillary hDMVEC subpopulation, while the remaining arterial hDMVEC subpopulation (EphB1 − ∕EphB4 − ) express ephrin-B2 ligands.…”

Section: Human Dermal Microvascular Endothelial Cell Culture and Tranmentioning

confidence: 99%

“…11 Recently, we found that EphB1 receptors and ephrin-B2 ligands are coexpressed on the lesional endothelial cells (ECs) in patients with port wine stains (PWSs). 12 Due to their abundance on a variety of cell types, Eph receptors and their ligands have become viable targets for therapeutic agents that can be conjugated to various targeting moieties including peptides, antibodies, and the ephrins themselves. [13][14][15][16][17][18][19][20] For example, Blevins et al 15 conjugated a peptide that targets EphA2 and EphA4 to a PEG linker and a polymer for the delivery of therapeutic plasmids to the pancreas.…”

Section: Introductionmentioning

confidence: 99%

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Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands

et al. 2019

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Over-or under-expression of erythropoietin-production human hepatocellular receptors (Eph) and their ligands are associated with various diseases. Therefore, these molecular biomarkers can potentially be used as binding targets for the delivery of therapeutic and/or imaging agents to cells characterized by such irregular expressions. We have engineered nanoparticles derived from erythrocytes and doped with the near-infrared (NIR) FDA-approved dye, indocyanine green. We refer to these nanoparticles as NIR erythrocyte-derived transducers (NETs). We functionalized the NETs with the ligand-binding domain of a particular Eph receptor, EphB1, to target the genetically modified human dermal microvascular endothelial cells (hDMVECs) with coexpression of EphB1 receptor and its ligand ephrin-B2. This cell model mimics the pathological phenotypes of lesional endothelial cells (ECs) in port wine stains (PWSs). Our quantitative fluorescence imaging results demonstrate that such functionalized NETs bind to the ephrin-B2 ligands on these hDMVECs in a dose-dependent manner that varies sigmoidally with the number density of the particles. These nanoparticles may potentially serve as agents to target PWS lesional ECs and other diseases characterized with over-expression of Eph receptors or their associated ligands to mediate phototherapy.

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Section: Human Dermal Microvascular Endothelial Cell Culture and Tranmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands

et al. 2019

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“…In the study by Tan et al . the authors investigate the anatomy of PWS capillaries and expression of developmental markers on ECs in PWS tissue samples.…”

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confidence: 93%

“…The paper by Tan et al . provides new evidence supporting the hypothesis that PWS is caused by disruption during development and that this affects EC phenotype.…”

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confidence: 93%

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B1 and B2: a role for ephrin signalling in port-wine stain

Fear

2017

Br J Dermatol

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Characterization of Laser‐Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy

Huang

Xiang

et al. 2019

Lasers Surg Med

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Background and Objectives Port wine stain (PWS) is a congenital vascular malformation of the human skin. Laser is the treatment of choice for PWS. Laser‐resistant PWS is one crucial factor accounting for inadequate treatment outcome, which needs to be fully characterized. This study aims to quantitatively characterize the morphology of laser‐resistant PWS blood vessels in the upper papillary dermis using in vivo reflectance confocal microscopy (RCM). Study Design/Materials and Methods A total of 42 PWS subjects receiving laser treatment from August 2016 through July 2018 were enrolled into this study. Thirty‐three subjects had facial PWS; nine had extremity PWS. All subject's PWS received multiplex 585/1,064 nm laser treatment. RCM images were taken before and after treatment. The density, diameter, blood flow, and depth of PWS blood vessels were analyzed. Results We found 44.4% PWS on the extremities (four out of nine subjects) were laser‐resistant, which was significantly higher (P < 0.001) when compared with those PWS on the face (15.2%, 5 out of 33 subjects). The laser‐resistant facial PWS blood vessels had significantly higher blood flow (1.35 ± 0.26 U vs. 0.89 ± 0.22 U, P < 0.001), larger blood vessel diameters (109.60 ± 18.24 µm vs. 84.36 ± 24.04 µm, P = 0.033) and were located deeper in the skin (106.01 ± 13.87 µm vs. 87.82 ± 12.57 µm, P < 0.001) in the skin when compared with laser‐responsive PWS on the face. The average PWS blood vessel density (17.01 ± 4.63/mm2 vs. 16.61 ± 4.44/mm2, P = 0.857) was not correlated to the laser resistance. Conclusions Laser‐resistant PWS blood vessels had significantly higher blood flow, larger diameters, and were located deeper in the skin. RCM can be a valuable tool for a prognostic evaluation on laser‐resistant lesions before treatment, thereby providing guidance for tailored laser treatment protocols, which may improve the therapeutic outcome. The limitations for this study include relative small sample size and acquisitions of different blood vessels before and after 2 months of treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

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Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation

Cited by 41 publications

References 47 publications

Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands

Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands

B1 and B2: a role for ephrin signalling in port-wine stain

Characterization of Laser‐Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy

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