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裸鼠体内由人肝海绵状血管瘤内皮细胞形成的异常血管适合于药物评价。

Abnormal blood vessels formed by human liver cavernous hemangioma endothelial cells in nude mice are suitable for drug evaluation.

机构信息

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, PR China.

出版信息

Microvasc Res. 2009 Dec;78(3):379-85. doi: 10.1016/j.mvr.2009.08.007. Epub 2009 Aug 31.

DOI:10.1016/j.mvr.2009.08.007
PMID:19729028
Abstract

Cavernous hemangioma is vascular malformation with developmental aberrations. It was assumed that the abnormality of endothelial cells contributed greatly to the occurrence of cavernous hemangioma. In our previous study, we have found distinct characteristics of endothelial cells derived from human liver cavernous hemangioma (HCHEC). Here, we reported the abnormal vascular vessels formed by primary HCHEC in nude mice and that the drug podophyllotoxin can destroy HCHEC in vitro and in vivo. HCHEC was isolated from a human liver cavernous hemangioma specimen, and the HCHEC generated a red hemangioma-like mass 7 days after subcutaneously co-inoculating HCHEC and human liver cancer cells (Bel-7402) in nude mice. Lentiviral expression of GFP and immunohistochemistry for human CD31 was used to confirm that the HCHEC formed the blood vessels in nude mice. And the pathological features of vascular vessels formed by HCHEC were very similar to clinical cavernous hemangioma. In addition, by MTT assay, the drug podophyllotoxin was found inhibiting HCHEC viability, and by TUNEL and DNA ladder assays, podophyllotoxin was found inducing apoptosis of HCHEC. Moreover, podophyllotoxin was also effective for destroying the abnormal vascular vessels in the hemangioma-like mass in nude mice. In summary, the HCHEC can form abnormal blood vessels in nude mice, and we can evaluate drugs for cavernous hemangioma by using HCHEC in vitro and in vivo.

摘要

海绵状血管瘤是具有发育异常的血管畸形。人们认为内皮细胞的异常对海绵状血管瘤的发生有很大的贡献。在我们之前的研究中,我们发现了源自人肝海绵状血管瘤(HCHEC)的内皮细胞的明显特征。在这里,我们报道了由原代 HCHEC 在裸鼠中形成的异常血管,以及鬼臼毒素药物可以在体外和体内破坏 HCHEC。HCHEC 是从人肝海绵状血管瘤标本中分离出来的,当 HCHEC 和人肝癌细胞(Bel-7402)在裸鼠皮下共接种时,HCHEC 在 7 天后生成了一个类似于血管瘤的红色肿块。利用慢病毒表达 GFP 和免疫组织化学检测人 CD31,证实了 HCHEC 在裸鼠中形成了血管。而且,HCHEC 形成的血管的病理特征与临床海绵状血管瘤非常相似。此外,通过 MTT 检测,发现鬼臼毒素抑制 HCHEC 的活力,通过 TUNEL 和 DNA 梯检测,发现鬼臼毒素诱导 HCHEC 凋亡。此外,鬼臼毒素对破坏裸鼠中血管瘤样肿块中的异常血管也很有效。总之,HCHEC 可以在裸鼠中形成异常血管,我们可以通过在体外和体内使用 HCHEC 来评估治疗海绵状血管瘤的药物。

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