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Three-Dimensional Microtumor Formation of Infantile Hemangioma-Derived Endothelial Cells for Mechanistic Exploration and Drug Screening

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机构: [1]Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China. [2]Med-X Center for Informatics, Sichuan University, Chengdu 610041, China. [3]Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, NHC, West China Hospital, Sichuan University, Chengdu 610041, China. [4]Pediatric Intensive Care Unit, Department of Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, China.
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关键词: drug screening infantile hemangioma three-dimensional microtumor model extracellular matrix

摘要:
Infantile hemangioma (IH) is the most prevalent type of vascular tumor in infants. The pathophysiology of IH is unknown. The tissue structure and physiology of two-dimensional cell cultures differ greatly from those in vivo, and spontaneous regression often occurs during tumor formation in nude mice and has severely limited research into the pathogenesis and development of IH. By decellularizing porcine aorta, we attempted to obtain vascular-specific extracellular matrix as the bioink for fabricating micropattern arrays of varying diameters via microcontact printing. We then constructed IH-derived CD31+ hemangioma endothelial cell three-dimensional microtumor models. The vascular-specific and decellularized extracellular matrix was suitable for the growth of infantile hemangioma-derived endothelial cells. The KEGG signaling pathway analysis revealed enrichment primarily in stem cell pluripotency, RAS, and PI3KAkt compared to the two-dimensional cell model according to RNA sequencing. Propranolol, the first-line medication for IH, was also used to test the model's applicability. We also found that metformin had some impact on the condition. The three-dimensional microtumor models of CD31+ hemangioma endothelial cells were more robust and efficient experimental models for IH mechanistic exploration and drug screening.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 3 区 药学 3 区 药物化学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 药物化学 3 区 药学
第一作者:
第一作者机构: [1]Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China. [2]Med-X Center for Informatics, Sichuan University, Chengdu 610041, China.
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通讯作者:
通讯机构: [1]Division of Oncology, Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu 610041, China. [2]Med-X Center for Informatics, Sichuan University, Chengdu 610041, China.
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