Department of Biomedical Engineering, College of Engineering Texas A&M University College Station TX.
Department of Medical Physiology College of MedicineTexas A&M Health Science Center Bryan TX.
J Am Heart Assoc. 2021 Nov 16;10(22):e022795. doi: 10.1161/JAHA.121.022795. Epub 2021 Nov 6.
Background Organ-on-chip technology has accelerated in vitro preclinical research of the vascular system, and a key strength of this platform is its promise to impact personalized medicine by providing a primary human cell-culture environment where endothelial cells are directly biopsied from individual tissue or differentiated through stem cell biotechniques. However, these methods are difficult to adopt in laboratories, and often result in impurity and heterogeneity of cells. This limits the power of organ-chips in making accurate physiological predictions. In this study, we report the use of blood-derived endothelial cells as alternatives to primary and induced pluripotent stem cell-derived endothelial cells. Methods and Results Here, the genotype, phenotype, and organ-chip functional characteristics of blood-derived outgrowth endothelial cells were compared against commercially available and most used primary endothelial cells and induced pluripotent stem cell-derived endothelial cells. The methods include RNA-sequencing, as well as criterion standard assays of cell marker expression, growth kinetics, migration potential, and vasculogenesis. Finally, thromboinflammatory responses under shear using vessel-chips engineered with blood-derived endothelial cells were assessed. Blood-derived endothelial cells exhibit the criterion standard hallmarks of typical endothelial cells. There are differences in gene expression profiles between different sources of endothelial cells, but blood-derived cells are relatively closer to primary cells than induced pluripotent stem cell-derived. Furthermore, blood-derived endothelial cells are much easier to obtain from individuals and yet, they serve as an equally effective cell source for functional studies and organ-chips compared with primary cells or induced pluripotent stem cell-derived cells. Conclusions Blood-derived endothelial cells may be used in preclinical research for developing more robust and personalized next-generation disease models using organ-on-chips.
背景 器官芯片技术加速了血管系统的体外临床前研究，该平台的一个主要优势是有望通过提供直接从个体组织中活检的内皮细胞或通过干细胞生物技术分化的原代细胞培养环境来影响个性化医疗。然而，这些方法在实验室中难以采用，并且常常导致细胞的杂质和异质性。这限制了器官芯片在进行准确生理预测方面的能力。在这项研究中，我们报告了使用血液衍生的内皮细胞作为替代物，替代原代和诱导多能干细胞衍生的内皮细胞。
方法和结果 在这里，比较了血液衍生的出芽内皮细胞的基因型、表型和器官芯片功能特征，与商业上可获得的和最常用的原代内皮细胞和诱导多能干细胞衍生的内皮细胞进行了比较。方法包括 RNA 测序以及细胞标志物表达、生长动力学、迁移潜能和血管生成的标准标准测定。最后，使用血管芯片评估了血液衍生的内皮细胞在剪切下的血栓炎症反应。
血液衍生的内皮细胞表现出典型内皮细胞的标准特征。不同来源的内皮细胞之间存在基因表达谱的差异，但血液衍生的细胞与原代细胞相比，与诱导多能干细胞衍生的细胞更为接近。此外，与原代细胞或诱导多能干细胞衍生的细胞相比，血液衍生的内皮细胞更容易从个体中获得，而且它们作为功能研究和器官芯片的有效细胞来源同样有效。
结论 血液衍生的内皮细胞可用于临床前研究，以使用器官芯片开发更强大和个性化的下一代疾病模型。
