Raka Mitra, Tracy K Hale, Helen L Fitzsimons, Clint Gray, Madeleine P J White
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引用次数: 0
Abstract
Infantile Haemangioma (IH) is vascular tumour in infants exhibiting rapid proliferation and angiogenesis followed by gradual involution.10% of cases are associated with disfiguring complications and requires medical interventions with β-blockers such as propranolol, surgery, or laser therapy. An in vitro IH three-dimensional (3D) model will improve our understanding of the disease mechanism(s). We have isolated and expanded CD31+ endothelial cells (HemEC) from patient-derived IH cell lines, and then grown as spheroids in StemDIFF Endothelial expansion media. These were then embedded in extracellular matrix hydrogel with reduced growth factors to initiate angiogenic sprouting. HemEC spheroids expressed CD31, GLUT1, VEGFR2, CD44, Vimentin, CD133 but not SMA, indicating their similarity to immature IH blood vessels and their angiogenic potential. Proteomic analysis revealed similar homology in terms of protein expression in spheroids and IH tissue. The high-throughput application of this 3D angiogenesis model was tested using propranolol to inhibit sprouting of spheroids with increased toxicity response. This study reports the development of a 3D model of IH that recapitulates angiogenic features of IH for molecular analysis and drug screening.
婴儿血管瘤(IH)是一种婴儿血管肿瘤,表现为快速增殖和血管生成,随后逐渐消退。10%的病例伴有毁容并发症,需要使用β受体阻滞剂(如普萘洛尔)、手术或激光治疗。体外 IH 三维(3D)模型将增进我们对疾病机制的了解。我们从患者来源的 IH 细胞系中分离并扩增出 CD31+ 内皮细胞(HemEC),然后在 StemDIFF 内皮细胞扩增培养基中培养成球状。然后将这些细胞包埋在含生长因子的细胞外基质水凝胶中,以启动血管新生发芽。HemEC 球体表达 CD31、GLUT1、VEGFR2、CD44、Vimentin、CD133,但不表达 SMA,这表明它们与未成熟的 IH 血管相似,并具有血管生成潜能。蛋白质组分析表明,球形组织和 IH 组织的蛋白质表达具有相似的同源性。该三维血管生成模型的高通量应用测试使用了普萘洛尔抑制球体萌发并增加毒性反应。本研究报告了IH三维模型的开发情况,该模型再现了IH的血管生成特征,可用于分子分析和药物筛选。
期刊介绍:
The British Journal of Dermatology (BJD) is committed to publishing the highest quality dermatological research. Through its publications, the journal seeks to advance the understanding, management, and treatment of skin diseases, ultimately aiming to improve patient outcomes.