肿瘤血管研究有一个长期的矛盾:血管给肿瘤供氧供能,是治疗的靶点;但血管同时又是药物进入肿瘤的必经通道,破坏它可能反而阻断给药。理解这个矛盾,需要能在体外把"肿瘤血管"和"正常血管"分开研究。
这里有两篇论文,恰好展示了两种典型用法。
一、把肿瘤血管当靶点:靶向 ICAM-1 的 CAR-T
Scientific Reports 2019;9:10634:Manufacturing and preclinical validation of CAR T cells targeting ICAM-1 for advanced thyroid cancer therapy(靶向 ICAM-1 的 CAR-T 细胞用于晚期甲状腺癌治疗的制备与临床前验证)。
ICAM-1(CD54)在多种肿瘤细胞与肿瘤相关血管内皮上高表达,在静息状态下的正常组织表达较低——这正是它作为靶点的理由。该研究完成了从载体制备到临床前验证的完整链条,使用的细胞包括 H-6053 人原代肺泡上皮细胞(作为正常组织/毒性评估的对照细胞)与 BALB-5053。
方法学启示:CAR-T 的临床前评价里,"对正常细胞的毒性"与"对靶细胞的杀伤"同等重要。用原代正常细胞做脱靶评估,比用细胞系更接近真实组织。

二、把血管当机制对象:Oct4 与血管生成
Nature Communications 2019;10:967:Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis(血管周细胞特异性敲除干细胞多能性基因 Oct4 抑制血管生成)。
研究使用 C57-6052 小鼠主动脉内皮细胞,验证了血管周细胞中 Oct4 对血管生成的调控作用。这条线索把"干细胞多能性因子"和"血管稳态"连了起来,也说明血管壁上的细胞不是被动结构。
方法学启示:基因敲除小鼠来源的原代内皮细胞,是"体内表型 → 体外机制"这条链条上最直接的验证材料。用 siRNA 敲低替代基因型敲除,在血管内皮上经常打不干净。
三、肿瘤相关内皮细胞(TEC)为什么难做,又为什么值得做
TEC 与正常组织内皮在形态、通透性、黏附分子表达、对 VEGF 的依赖性上都不同——它更"漏"、更无序、更依赖旁分泌。但 TEC 极难从临床标本中分离:肿瘤组织酶解后内皮细胞占比很低,且容易混入肿瘤细胞与成纤维细胞。
这也是为什么"有现货 TEC"很关键:它把"能不能拿到足够数量的肿瘤来源内皮"这个问题,从实验风险变成了采购问题。
Cell Biologics 的肿瘤相关内皮细胞与人、小鼠的正常内皮细胞并列供应,可做同源对照:
对照设计 | 目的 |
肿瘤相关内皮 vs 正常组织内皮 | 评估药物对"异常血管"的选择性 |
人源 TEC vs 小鼠 TEC | 跨物种验证,衔接体内模型 |
TEC + 肿瘤相关成纤维(TAF)共培养 | 重建肿瘤微环境的旁分泌网络 |
四、一句话总结
血管生成研究的体外部分,成败往往不在检测方法,而在细胞选得对不对、对照配得齐不齐。
本产品仅供科研使用(RUO),不用于人体、临床诊断或治疗用途。文献信息引自公开发表的论文。
Cell Biologics 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