更新于：2024-11-01

VEGFR2 x EFNB2

更新于：2024-11-01

基本信息

关联

项与 VEGFR2 x EFNB2 相关的药物

BO-011

靶点

EFNB2 x VEGFR2

作用机制

EFNB2 inhibitors [+1]

在研机构-

原研机构

Highlight Therapeutics SL

在研适应症-

非在研适应症

肿瘤

最高研发阶段终止

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 VEGFR2 x EFNB2 相关的临床结果

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100 项与 VEGFR2 x EFNB2 相关的转化医学

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0 项与 VEGFR2 x EFNB2 相关的专利（医药）

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项与 VEGFR2 x EFNB2 相关的文献（医药）

2023-07-01·BioImpacts

Differentiation and molecular characterization of endothelial progenitor and vascular smooth muscle cells from induced pluripotent stem cells

Article

作者: Dastouri, Mohammadreza ; Akar, Ahmet Ruchan ; Ozdag, Hilal ; Can, Alp

Introduction: Pluripotent stem cells have been used by various researchers to differentiate and characterize endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) for the clinical treatment of vascular injuries. Studies continue to differentiate and characterize the cells with higher vascularization potential and low risk of malignant transformation to the recipient. Unlike previous studies, this research aimed to differentiate induced pluripotent stem (iPS) cells into endothelial progenitor cells (EPCs) and VSMCs using a step-wise technique. This was achieved by elucidating the spatio-temporal expressions of the stage-specific genes and proteins during the differentiation process. The presence of highly expressed oncogenes in iPS cells was also investigated during the differentiation period. Methods: Induced PS cells were differentiated into lateral mesoderm cells (Flk1+). The Flk1+ populations were isolated on day 5.5 of the mesodermal differentiation period. Flk1+ cells were further differentiated into EPCs and VSMCs using VEGF165 and platelet-derived growth factor-BB (PDGF-BB), respectively, and then characterized using gene expression levels, immunocytochemistry (ICC), and western blot (WB) methods. During the differentiation steps, the expression levels of the marker genes and proto-oncogenic Myc and Klf4 genes were simultaneously studied. Results: The optimal time for the isolation of Flk1+ cells was on day 5.5. EPCs and VSMCs were differentiated from Flk1+ cells and characterized with EPC-specific markers, including Kdr, Pecam1, CD133, Cdh5, Efnb2, Vcam1; and VSMC-specific markers, including Acta2, Cnn1, Des, and Myh11. Differentiated cells were validated based on their temporal gene expressions, protein synthesis, and localization at certain time points. Significant decreases in Myc and Klf4 gene expression levels were observed during the EPCs and VSMC differentiation period. Conclusion: EPCs and VSMCs were successfully differentiated from iPS cells and characterized by gene expression levels, ICC, and WB. We observed significant decreases in oncogene expression levels in the differentiated EPCs and VSMCs. In terms of safety, the described methodology provided a better safety margin. EPCs and VSMC obtained using this method may be good candidates for transplantation and vascular regeneration.

2023-04-05·Advances in experimental medicine and biology

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Enhance Angiogenesis Through Upregulation of the VWF and Flk1 Genes in Endothelial Cells.

Article

作者: Vu, Ngoc Bich ; Van Pham, Phuc ; Huynh, Phat Duc

INTRODUCTIONExosomes derived from mesenchymal stem cells (MSCs) are crucial mediators of the paracrine effects as well as tissue repair and have promising clinical applications. They enhance tissue regeneration by reducing inflammatory responses, enhancing proliferation, inhibiting apoptosis, and stimulating angiogenesis. This study aimed to evaluate the mechanism of angiogenesis supported by exosomes derived from MSCs.METHODSExosomes were isolated via ultracentrifugation of a conditioned medium collected from human umbilical cord MSC (hUCMSC) cultures. These exosomes were characterized using transmission electron microscopy, and the expression of specific markers (CD9, CD81, and CD63) was evaluated. To understand the mechanism of angiogenesis, we evaluated the effects of exosomes in endothelial cells (HUVECs). The obtained exosomes were supplemented at a dose of 20 μg/mL into two kinds of culture media for HUVECs (M200 medium and endothelial cell growth medium), while phosphate-buffered saline was added to these media as a control. The effects of the exosomes were evaluated based on the formation of a tubular structure in the culture and the expression of angiogenic genes (MMP-2, Ephrin B2, Ephrin B4, Flk1, Flt1, VWF, VE-cadherin, CD31, ANG1, ANG2, and HGF) via RT-PCR.RESULTSThe exosomes were obtained from the hUCMSCs at a concentration of 0.7 ± 0.029 μg/mL. They accelerated the formation of new blood vessels by upregulating HGF, VWF, CD31, Flt1, and Flk1 (especially VWF and Flt1).CONCLUSIONExosomes derived from hUCMSCs can promote angiogenesis through upregulation of VWF and Flt1 in endothelial cells.

2022-02-01·Pathology - Research and Practice4区 · 医学

Vasohibin-1 and -2 in pulmonary lymphangioleiomyomatosis (LAM) cells associated with angiogenic and prognostic factors

4区 · 医学

Article

作者: Inoue, Chihiro ; Okada, Yoshinori ; Miki, Yasuhiro ; Seyama, Kuniaki ; Saito-Koyama, Ryoko ; Kobayashi, Kazuma ; Sasano, Hironobu

Lymphangioleiomyomatosis (LAM) is a rare pulmonary neoplasm, clinically associated with dyspnea and respiratory failure. Current therapeutic modalities do not necessarily reach satisfactory outcome and novel therapeutic approaches are currently warranted. Therefore, in this study, we focused on vasohibin-1 (VASH1) and -2 (VASH2); VASH1 terminated and VASH2 promoted angiogenesis. In addition, both VASH1/2 were reported to influence the progression of various human malignancies. We first performed hierarchical clustering analysis to attempt to classify 36 LAM cases into three different clusters according to immunoreactivity of VASH1/2 and other angiogenic and prognostic factors of LAM; VEGFR1/2/3, p-mTOR, p-S6, p-4EBP, ERα, PgR, MMP2, and MMP9. The cluster harboring higher angiogenic factors had higher VASH1/2 status. VASH1 was significantly positively correlated with VEGFR2, MMP9, and p-mTOR (p-value <0.05), and VASH2 with both angiogenic and prognostic factors including VEGFR1, PgR, MMP9, p-mTOR, p-S6, and p-4EBP (p-value <0.05). Subsequent PCR array of angiogenic genes demonstrated that high VASH1 mRNA was significantly positively associated with the status of SPHK1 and TYPM, lower EGF and EFNB2 (p-value <0.05), and high VASH2 mRNA negatively with MMP2 (p-value <0.05). VASH1 was considered to be up-regulated by activation of angiogenesis, whereas VASH2 could influence the angiogenesis and progression of LAM.