Abstract：
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.
摘要：
基于水凝胶的3D细胞培养物可以在体外概括(病理)生理现象。然而,由于它们复杂的多因素调节，使这些组织和疾病模型适应高通量筛查工作流程仍然具有挑战性.在这项研究中,一种新的精确文化缩放（PCS-X）方法将统计技术（实验设计和多元线性回归）与自动化，并行实验和分析，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生成培养物。细胞密度的变化，系统地探索了生长因子的补充和培养基组成，以在384孔板格式的间充质基质细胞或视网膜微血管周细胞的内皮单培养物和共培养物中诱导血管生成。已开发的培养物显示以复合和剂量依赖性方式对血管生成抑制剂作出反应，展示了PCS-X在创建用于药物发现和个体化治疗的平行组织和疾病模型方面的范围和能力。本文受版权保护。保留所有权利。
