A novel quantitative angiogenesis assay based on visualized vascular organoid

IF 9.2 1区医学 Q1 PERIPHERAL VASCULAR DISEASE Angiogenesis Pub Date : 2025-01-03 DOI:10.1007/s10456-024-09967-z

Yun Zhao, Mengze Sun, Zihang Pan, Weijing Kong, Zixuan Hong, Wei Zhang, Bingbing Sun, Jingjing Zhang, Xi Wang, Kai Wang

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Abstract

Angiogenesis describes the sprouting of blood vessels from existing vasculatures and it plays a pivotal role in disease progress such as diabetes, age-related macular degeneration and cancer. However, the most widely used anti-angiogenic agents targeting vascular endothelial growth factor (VEGF) pathway still lacked of specificity and therapeutic efficacy. To establish a method suitable for high-throughput drug screening and faithfully recapitulate the feature of in vivo angiogenesis, we generated a PECAM1-mRuby3-secNluc; ACTA2-EGFP dual reporter human pluripotent stem cell (hPSC) line and utilizing the cell line to establish a visualized and quantifiable in vitro angiogenesis model with stem cell-derived vascular organoid. Using this method, we evaluated the anti-angiogenic effect of VEGFR inhibitor and efficiently identified several potential candidates of pro- and anti-angiogenic therapy via bioluminescence-based quantification. Overall, our study provides a valuable platform for in vitro drug screenings.

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一种基于可视化血管类器官的新型定量血管生成实验

血管生成是指血管从现有的血管系统中发芽，它在糖尿病、年龄相关性黄斑变性和癌症等疾病的进展中起着关键作用。然而，目前应用最广泛的靶向血管内皮生长因子（VEGF）通路的抗血管生成药物仍缺乏特异性和治疗效果。为了建立一种适合于高通量药物筛选的方法，并忠实地再现体内血管生成的特征，我们生成了PECAM1-mRuby3-secNluc；ACTA2-EGFP双报告细胞人多能干细胞（hPSC）系，并利用该细胞系建立可视化、可量化的干细胞衍生血管类器官体外血管生成模型。利用这种方法，我们评估了VEGFR抑制剂的抗血管生成作用，并通过基于生物发光的量化有效地确定了几种潜在的促血管生成和抗血管生成治疗候选药物。总之，我们的研究为体外药物筛选提供了一个有价值的平台。

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来源期刊

Angiogenesis PERIPHERAL VASCULAR DISEASE-

CiteScore

21.90

自引率

8.20%

发文量

审稿时长

6-12 weeks

期刊介绍： Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.