PDF(Pubmed)
Abstract：
The function of the glomerulus depends on the complex cell-cell/matrix interactions and replication of this in vitro would aid biological understanding in both health and disease. Previous models do not fully reflect all cell types and interactions present as they overlook mesangial cells within their 3D matrix. Herein, the development of a microphysiological system that contains all resident renal cell types in an anatomically relevant manner is presented. A detailed transcriptomic analysis of the contributing biology of each cell type, as well as functionally appropriate albumin retention in the system, is demonstrated. The important role of mesangial cells is shown in promoting the health and maturity of the other cell types. Additionally, a comparison of the incremental advances that each individual cell type brings to the phenotype of the others demonstrates that glomerular cells in simple 2D culture exhibit a state more reflective of the dysfunction observed in human disease than previously recognized. This in vitro model will expand the capability to investigate glomerular biology in a more translatable manner by the inclusion of the important mesangial cell compartment.
摘要：
肾小球的功能取决于复杂的细胞-细胞/基质相互作用，这种相互作用在体外的复制将有助于健康和疾病的生物学理解。以前的模型不能完全反映所有细胞类型和存在的相互作用，因为它们忽略了3D矩阵中的系膜细胞。在这里，提出了以解剖学相关方式包含所有驻留肾细胞类型的微生理系统的发展。对每种细胞类型的生物学贡献进行了详细的转录组学分析，以及系统中功能适当的白蛋白滞留，已证明。肾小球膜细胞的重要作用是促进其他细胞类型的健康和成熟。此外,对每种单个细胞类型给其他细胞类型的表型带来的递增进步的比较表明，在简单的2D培养中，肾小球细胞表现出比以前认识到的更能反映人类疾病中观察到的功能障碍的状态。这种体外模型将通过包含重要的肾小球系膜细胞区室来扩大以更可翻译的方式研究肾小球生物学的能力。
