Journal Article

ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo

Lu, Hongxu, Beretov, Julia, Cox, Thomas R., Boyle, Sarah T., Martelotto, Luciano, Tipper, Joanne L., Valdes‐Mora, Fatima, Fuente, Laura Rodriguez de la, Samuel, Michael S., Ormandy, Christopher J., Castillo, Lesley, Millar, Ewan K. A., Skhinas, Joanna N., Law, Andrew M. K., Huang, Robert J., Tavakoli, Javad, Fang, Guocheng, Chen, Jiamin, Rossello, Fernando J., Ji, Hanlee P., Colino‐Sanguino, Yolanda, Grimes, Susan M., Jin, Dayong, Gallego‐Ortega, David, Venhuizen, Jeron

2022

Overview

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. Alginate‐based tissue engineering (ALTEN) enables three‐dimensional (3D) ex vivo culture of explanted tissue biopsies. This method recapitulates the original characteristics of the source tissue's cellular niches with high‐fidelity, including cellular diversity, extracellular matrix (ECM), and their molecular milieu. ALTEN enables rapid and faithful characterization drugs effects in explanted tumoroids as n‐of‐one clinical trials with potential use in personalized medicine.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: alginate / Apoptosis / Biopsy / ex vivo drug screening / Flow cytometry / Histology / Homeostasis / Hydrogels / Machine Elements / Maskinelement / Microscopy / single-cell RNAseq / three dimensional culture / three dimensionalculture / Tissue engineering / tissue microenvironment / Tumors / whole-tissue organoids