Li Yanan, Wang Chuan, Li Yi, Zhu Xinglong, Bao Ji, Ji Yi
Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China.
Department of Respiratory and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2025 Aug 14;13:1629770. doi: 10.3389/fcell.2025.1629770. eCollection 2025.
Congenital hemangiomas are rare vascular anomalies that manifest at birth. Noninvoluting congenital hemangiomas present significant clinical challenges due to their persistence and associated complications. The mechanisms underlying congenital hemangiomas remain poorly understood, and current treatments have shown limited efficacy. This study aims to explore potential therapeutic strategies through the establishment of a stable cell model derived from noninvoluting congenital hemangiomas.
Primary cells were isolated from noninvoluting congenital hemangioma tissue obtained from five patients, and CD31-positive endothelial cells were cultured and characterized. A subcutaneous xenograft model was established in nude mice to investigate tumorigenicity and evaluate the effects of various drugs, including bleomycin and sirolimus.
CD31-positive noninvoluting congenital hemangioma endothelial cells were successfully cultured and formed spheroids , demonstrating distinct morphological and immunohistochemical characteristics. When injected into nude mice, CD31-positive noninvoluting congenital hemangioma endothelial cells developed into tumors, whereas primary noninvoluting congenital hemangioma cells did not. Drug testing revealed that bleomycin and sirolimus effectively inhibited CD31-positive noninvoluting congenital hemangioma endothelial cells proliferation, with combination therapy showing significant tumor regression .
The development of a stable cell model for noninvoluting congenital hemangiomas provides a valuable platform for understanding their pathogenesis and evaluating therapeutic options. The combination of bleomycin and sirolimus demonstrates promise as a novel treatment strategy, potentially improving outcomes for patients with noninvoluting congenital hemangiomas. Further studies are needed to explore the molecular mechanisms involved and to assess the efficacy across different congenital hemangioma subtypes.
先天性血管瘤是罕见的血管异常，出生时即出现。非消退性先天性血管瘤因其持续存在及相关并发症而带来重大临床挑战。先天性血管瘤的发病机制仍知之甚少，目前的治疗效果有限。本研究旨在通过建立源自非消退性先天性血管瘤的稳定细胞模型来探索潜在的治疗策略。
从5例患者的非消退性先天性血管瘤组织中分离原代细胞，培养并鉴定CD31阳性内皮细胞。在裸鼠中建立皮下异种移植模型，以研究致瘤性并评估包括博来霉素和西罗莫司在内的各种药物的效果。
成功培养出CD31阳性的非消退性先天性血管瘤内皮细胞并形成球体，显示出独特的形态和免疫组化特征。将其注射到裸鼠体内时，CD31阳性的非消退性先天性血管瘤内皮细胞会发展成肿瘤，而原代非消退性先天性血管瘤细胞则不会。药物测试表明，博来霉素和西罗莫司可有效抑制CD31阳性的非消退性先天性血管瘤内皮细胞增殖，联合治疗显示出显著的肿瘤消退。
非消退性先天性血管瘤稳定细胞模型的建立为理解其发病机制和评估治疗选择提供了一个有价值的平台。博来霉素和西罗莫司的联合使用显示出作为一种新治疗策略的前景，可能改善非消退性先天性血管瘤患者的治疗效果。需要进一步研究以探索其中涉及的确切分子机制，并评估对不同先天性血管瘤亚型的疗效。
