Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Chin Med J (Engl). 2013 Jan;126(1):88-94.
Infantile hemangioma (IH) is the most common benign tumor in children with prevalence in the face and neck. Various treatment options including oral propranolol have been described for IH, but the mechanism of drugs remains enigmatic. The aim of this study was to investigate the pathogenesis and establish a reliable in vivo model of IH which can provide platform for drug exploration.
Stem cells from the proliferating hemangiomas (HemSCs) were isolated by CD133-tagged immunomagnetic beads. Their phenotype and angiogenic property were investigated by flow cytometry, culturing on Matrigel, real-time polymerase chain reaction (PCR), immunofluorescent staining and injection into BALB/c-nu mice.
HemSCs had robust ability of proliferating and cloning. The time of cells doubling in proliferative phase was 16 hours. Flow cytometry showed that HemSCs expressed mesenchymal markers CD29, CD44, but not endothelial/hematopoietic marker of CD34 and hematopoietic marker CD45. The expression of CD105 was much lower than that of the reported hemangioma derived or normal mesenchymal stem cell (MSC). Real-time PCR showed that the mRNA levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-1 (MMP-1) of HemSCs were higher than that of neonatal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). After HemSCs were cultured on Matrigel in vitro, they formed tube-like structure in a short time (16 hours) and differentiated into endothelial cells in 7 days. After 1 - 2 weeks of implantation into immunodeficient mice, HemSCs generated glucose transporter 1 positive blood vessels. When co-injected with HUVECs, the vascularization of HemSCs was greatly enhanced. However, the single implantation of HUVECs hardly formed blood vessels in BALB/c-nu mice (P < 0.05).
HemSCs may be some kinds of primitive mesoderm derived stem cells with powerful angiogenic ability, which can recapitulate human hemangioma by co-injecting into immunodeficient mice with HUVECs.
婴儿血管瘤（IH）是儿童中最常见的良性肿瘤，好发于面颈部。目前已有多种治疗方法被用于 IH，包括口服普萘洛尔，但药物的作用机制仍不清楚。本研究旨在探讨其发病机制，并建立一种可靠的 IH 体内模型，为药物探索提供平台。
通过 CD133 标记免疫磁珠分离增殖性血管瘤中的干细胞（HemSCs）。通过流式细胞术、Matrigel 培养、实时聚合酶链反应（PCR）、免疫荧光染色和注射到 BALB/c-nu 小鼠中来研究其表型和血管生成特性。
HemSCs 具有强大的增殖和克隆能力。增殖期细胞倍增时间为 16 小时。流式细胞术显示，HemSCs 表达间充质标志物 CD29、CD44，但不表达内皮/造血标志物 CD34 和造血标志物 CD45。CD105 的表达远低于报道的血管瘤来源或正常间充质干细胞（MSC）。实时 PCR 显示，HemSCs 的血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）和基质金属蛋白酶-1（MMP-1）mRNA 水平均高于新生儿人真皮成纤维细胞（NHDFs）和人脐静脉内皮细胞（HUVECs）。HemSCs 在体外 Matrigel 上培养后，在短时间内（16 小时）形成管状结构，并在 7 天内分化为内皮细胞。在免疫缺陷小鼠中植入 1-2 周后，HemSCs 产生葡萄糖转运蛋白 1 阳性血管。当与 HUVECs 共注射时，HemSCs 的血管生成能力大大增强。然而，单独注射 HUVECs 几乎不能在 BALB/c-nu 小鼠中形成血管（P<0.05）。
HemSCs 可能是具有强大血管生成能力的原始中胚层来源的干细胞，通过与 HUVECs 共注射到免疫缺陷小鼠中，可以重现人类血管瘤。
