{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:04:53Z","timestamp":1788887093598,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["NRF-2022R1I1A3069687"],"award-info":[{"award-number":["NRF-2022R1I1A3069687"]}]},{"name":"Ministry of Education","award":["2023R1A2C2004906"],"award-info":[{"award-number":["2023R1A2C2004906"]}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["NRF-2022R1I1A3069687"],"award-info":[{"award-number":["NRF-2022R1I1A3069687"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Korean government (MSIT)","doi-asserted-by":"publisher","award":["2023R1A2C2004906"],"award-info":[{"award-number":["2023R1A2C2004906"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 VEGF, ANG2, FSTL1, and MARCKS, decreased; in comparison, CSPG4, 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 \u03b1-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\u2019 pathology and support the development of personalized therapies.<\/jats:p>","DOI":"10.3390\/cells14141081","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T15:01:05Z","timestamp":1752591665000},"page":"1081","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modeling Aberrant Angiogenesis in Arteriovenous Malformations Using Endothelial Cells and Organoids for Pharmacological Treatment"],"prefix":"10.3390","volume":"14","author":[{"given":"Eun Jung","family":"Oh","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-4836","authenticated-orcid":false,"given":"Hyun Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suin","family":"Kwak","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Yun","family":"Chung","sequence":"additional","affiliation":[{"name":"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"},{"name":"BK21 FOUR KNU Convergence Educational Program of Biomedical Science for Creative Future Talents, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100629","DOI":"10.1016\/j.tvir.2019.100629","article-title":"Practical genetic and biologic therapeutic considerations in vascular anomalies","volume":"22","author":"Adams","year":"2019","journal-title":"Tech. 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