Oh Eun Jung, Kim Hyun Mi, Kwak Suin, Chung Ho Yun
Department of Plastic and Reconstructive Surgery, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Cells. 2025 Jul 15;14(14):1081. doi: 10.3390/cells14141081.
Arteriovenous malformations (AVMs) are congenital vascular anomalies defined by abnormal direct connections between arteries and veins due to their complex structure or endovascular approaches. Pharmacological strategies targeting the underlying molecular mechanisms are thus gaining increasing attention in an effort to determine the mechanism involved in AVM regulation. In this study, we examined 30 human tissue samples, comprising 10 vascular samples, 10 human fibroblasts derived from AVM tissue, and 10 vascular samples derived from healthy individuals. The pharmacological agents thalidomide, U0126, and rapamycin were applied to the isolated endothelial cells (ECs). The pharmacological treatments reduced the proliferation of AVM ECs and downregulated miR-135b-5p, a biomarker associated with AVMs. The expression levels of angiogenesis-related genes, including , , , and , decreased; in comparison, , a gene related to capillary networks, was upregulated. Following analysis of these findings, skin samples from 10 AVM patients were reprogrammed into induced pluripotent stem cells (iPSCs) to generate AVM blood vessel organoids. Treatment of these AVM blood vessel organoids with thalidomide, U0126, and rapamycin resulted in a reduction in the expression of the EC markers CD31 and α-SMA. The establishment of AVM blood vessel organoids offers a physiologically relevant in vitro model for disease characterization and drug screening. The authors of future studies should aim to refine this model using advanced techniques, such as microfluidic systems, to more efficiently replicate AVMs' pathology and support the development of personalized therapies.
动静脉畸形（AVM）是先天性血管异常，因其复杂的结构或血管内途径，由动脉与静脉之间异常的直接连接所定义。因此，针对潜在分子机制的药理学策略在确定参与AVM调节的机制方面正日益受到关注。在本研究中，我们检查了30个人体组织样本，包括10个血管样本、10个源自AVM组织的人成纤维细胞以及10个源自健康个体的血管样本。将沙利度胺、U0126和雷帕霉素等药物应用于分离的内皮细胞（EC）。药物治疗降低了AVM EC的增殖，并下调了与AVM相关的生物标志物miR-135b-5p。包括[此处原文缺失相关基因名称]等血管生成相关基因的表达水平降低；相比之下，与毛细血管网络相关的基因[此处原文缺失相关基因名称]上调。分析这些发现后，将10名AVM患者的皮肤样本重编程为诱导多能干细胞（iPSC），以生成AVM血管类器官。用沙利度胺、U0126和雷帕霉素处理这些AVM血管类器官，导致EC标志物CD31和α-SMA的表达降低。AVM血管类器官的建立为疾病特征描述和药物筛选提供了一个生理相关的体外模型。未来研究的作者应旨在使用先进技术（如微流控系统）完善该模型，以更有效地复制AVM的病理学并支持个性化疗法的开发。
