Department of Mechanical Engineering, KAIST, Daejeon 34141, Korea.
Lab Chip. 2022 Nov 8;22(22):4335-4348. doi: 10.1039/d2lc00597b.
A tumor is composed of heterogeneous cell population, which is known as tumor stroma. In particular, blood vessels have an indispensable role in the tumor microenvironment acting as a key player in anti-cancer drug delivery. Recently, efforts have been made to accurately recapitulate the microenvironment by employing distinct cell types, however, the proper formation of perfusable tumor tissue is challenging. Here, perfusable tumor tissue is engineered by implanting multicellular tumor spheroids inside the microfluidic devices. Blood perfusion, spheroid growth, and vascular dynamics were monitored according to the spheroid composition and the contribution of internal and external vascular cells to spheroid perfusion was analyzed. Most notably, the increased penetration depth of fluorescence conjugated anti-cancer drug was observed in tri-culture spheroids. The implementation of tumor microenvironment reconstruction developed in this study not only creates a perfusable tumor vascular model but can also be utilized as a novel drug screening platform with patient-derived samples.
肿瘤由异质细胞群组成，称为肿瘤基质。特别是，血管在肿瘤微环境中具有不可或缺的作用，是抗癌药物输送的关键因素。最近，人们努力通过使用不同的细胞类型来准确再现微环境，然而，可灌注肿瘤组织的适当形成具有挑战性。在这里，通过将多细胞肿瘤球体植入微流控设备中来构建可灌注的肿瘤组织。根据球体的组成以及内部和外部血管细胞对球体灌注的贡献来监测血液灌注、球体生长和血管动力学。值得注意的是，在三培养球体中观察到荧光标记抗癌药物的渗透深度增加。本研究中开发的肿瘤微环境重建的实施不仅创建了可灌注的肿瘤血管模型，而且还可以用作具有患者来源样本的新型药物筛选平台。
