Law Andrew M K, Chen Jiamin, Colino-Sanguino Yolanda, Fuente Laura Rodriguez de la, Fang Guocheng, Grimes Susan M, Lu Hongxu, Huang Robert J, Boyle Sarah T, Venhuizen Jeron, Castillo Lesley, Tavakoli Javad, Skhinas Joanna N, Millar Ewan K A, Beretov Julia, Rossello Fernando J, Tipper Joanne L, Ormandy Christopher J, Samuel Michael S, Cox Thomas R, Martelotto Luciano, Jin Dayong, Valdes-Mora Fatima, Ji Hanlee P, Gallego-Ortega David
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia.
Division of Oncology, Department of Medicine, Stanford University, California, 94305, USA.
Adv Sci (Weinh). 2022 Jul;9(21):e2103332. doi: 10.1002/advs.202103332. Epub 2022 May 25.
To fully investigate cellular responses to stimuli and perturbations within tissues, it is essential to replicate the complex molecular interactions within the local microenvironment of cellular niches. Here, the authors introduce Alginate-based tissue engineering (ALTEN), a biomimetic tissue platform that allows ex vivo analysis of explanted tissue biopsies. This method preserves the original characteristics of the source tissue's cellular milieu, allowing multiple and diverse cell types to be maintained over an extended period of time. As a result, ALTEN enables rapid and faithful characterization of perturbations across specific cell types within a tissue. Importantly, using single-cell genomics, this approach provides integrated cellular responses at the resolution of individual cells. ALTEN is a powerful tool for the analysis of cellular responses upon exposure to cytotoxic agents and immunomodulators. Additionally, ALTEN's scalability using automated microfluidic devices for tissue encapsulation and subsequent transport, to enable centralized high-throughput analysis of samples gathered by large-scale multicenter studies, is shown.
为了全面研究细胞对组织内刺激和扰动的反应，在细胞龛的局部微环境中复制复杂的分子相互作用至关重要。在此，作者介绍了基于藻酸盐的组织工程（ALTEN），这是一种仿生组织平台，可对取出的组织活检进行离体分析。该方法保留了源组织细胞环境的原始特征，使多种不同类型的细胞能够长时间维持。因此，ALTEN能够快速且准确地表征组织内特定细胞类型的扰动。重要的是，利用单细胞基因组学，这种方法能够在单个细胞的分辨率下提供整合的细胞反应。ALTEN是分析细胞暴露于细胞毒性剂和免疫调节剂后反应的强大工具。此外，还展示了ALTEN利用自动化微流控设备进行组织封装和后续运输的可扩展性，以实现对大规模多中心研究收集的样本进行集中高通量分析。
