Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, 01069, Dresden, Germany.
Medical Clinic I, University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307, Dresden, Germany.
Adv Healthc Mater. 2024 Jul;13(18):e2400388. doi: 10.1002/adhm.202400388. Epub 2024 Mar 22.
Hydrogel-based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high-throughput screening workflows remains challenging. In this study, a new precision culture scaling (PCS-X) methodology combines statistical techniques (design of experiment and multiple linear regression) with automated, parallelized experiments and analyses to customize hydrogel-based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells. Variations of cell density, growth factor supplementation, and media composition are systematically explored to induce vasculogenesis in endothelial mono- and cocultures with mesenchymal stromal cells or retinal microvascular pericytes in 384-well plate formats. The developed cultures are shown to respond to vasculogenesis inhibitors in a compound- and dose-dependent manner, demonstrating the scope and power of PCS-X in creating parallelized tissue and disease models for drug discovery and individualized therapies.
基于水凝胶的 3D 细胞培养可以在体外再现（病理）生理现象。然而，由于其复杂的多因素调节，将这些组织和疾病模型适应高通量筛选工作流程仍然具有挑战性。在这项研究中，一种新的精密培养缩放（PCS-X）方法结合了统计技术（实验设计和多元线性回归）以及自动化、并行化的实验和分析，使用人脐静脉内皮细胞和视网膜微血管内皮细胞定制基于水凝胶的血管发生培养物。系统地探索了细胞密度、生长因子补充和培养基组成的变化，以在 384 孔板格式中诱导内皮细胞单培养物和共培养物与间充质基质细胞或视网膜微血管周细胞的血管发生。所开发的培养物对血管发生抑制剂表现出化合物和剂量依赖性反应，证明了 PCS-X 在创建用于药物发现和个体化治疗的并行组织和疾病模型方面的范围和能力。
