Del Rocío Aguilera-Marquez Janette, Manzanares-Guzmán Alejandro, García-Uriostegui Lorena, Canales-Aguirre Alejandro A, Camacho-Villegas Tanya A, Lugo-Fabres Pavel H
Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Guadalajara 44270, Mexico.
SECIHTI-Secretaría de Ciencia, Humanidades, Tecnología e Innovación-Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara 44430, Mexico.
Gels. 2025 Apr 2;11(4):263. doi: 10.3390/gels11040263.
Glioblastoma (GBM) is a highly aggressive and malignant brain tumor, characterized by hypoxia in its microenvironment, which drives its growth and resistance to treatments. Hypoxia-inducible factor 1 (HIF-1) plays a central role in GBM progression by regulating cellular adaptation to low oxygen availability, promoting processes such as angiogenesis and cell invasion. However, studying and modeling GBM under hypoxic conditions is complex, especially due to the limitations of animal models. In this study, we developed a glioma spheroid model using an alginate-gelatin hydrogel scaffold, which enabled the simulation of hypoxic conditions within the tumor. The scaffold-based model demonstrated high reproducibility, facilitating the analysis of HIF-1α expression, a key protein in the hypoxic response of GBM. Furthermore, cell viability, the microstructural features of the encapsulated spheroids, and the water absorption rate of the hydrogel were assessed. Our findings validate the three-dimensional (3D) glioblastoma spheroids model as a valuable platform for studying hypoxia in GBM and evaluating new therapies. This approach could offer a more accessible and specific alternative for studying the tumor microenvironment and therapeutic resistance in GBM.
胶质母细胞瘤（GBM）是一种极具侵袭性和恶性的脑肿瘤，其微环境具有缺氧特征，这推动了肿瘤的生长和对治疗的抵抗。缺氧诱导因子1（HIF-1）通过调节细胞对低氧环境的适应，在GBM进展中发挥核心作用，促进血管生成和细胞侵袭等过程。然而，在缺氧条件下研究和模拟GBM很复杂，尤其是由于动物模型的局限性。在本研究中，我们使用藻酸盐-明胶水凝胶支架开发了一种胶质瘤球体模型，该模型能够模拟肿瘤内的缺氧条件。基于支架的模型显示出高重现性，便于分析HIF-1α的表达，HIF-1α是GBM缺氧反应中的关键蛋白。此外，还评估了细胞活力、封装球体的微观结构特征以及水凝胶的吸水率。我们的研究结果验证了三维（3D）胶质母细胞瘤球体模型是研究GBM缺氧和评估新疗法的宝贵平台。这种方法可为研究GBM的肿瘤微环境和治疗抵抗提供更易获取且更具特异性的替代方案。
