Advanced Science (Jul 2022)
ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo
- Andrew M. K. Law,
- Jiamin Chen,
- Yolanda Colino‐Sanguino,
- Laura Rodriguez de la Fuente,
- Guocheng Fang,
- Susan M. Grimes,
- Hongxu Lu,
- Robert J. Huang,
- Sarah T. Boyle,
- Jeron Venhuizen,
- Lesley Castillo,
- Javad Tavakoli,
- Joanna N. Skhinas,
- Ewan K. A. Millar,
- Julia Beretov,
- Fernando J. Rossello,
- Joanne L. Tipper,
- Christopher J. Ormandy,
- Michael S. Samuel,
- Thomas R. Cox,
- Luciano Martelotto,
- Dayong Jin,
- Fatima Valdes‐Mora,
- Hanlee P. Ji,
- David Gallego‐Ortega
Affiliations
- Andrew M. K. Law
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Jiamin Chen
- Division of Oncology Department of Medicine Stanford University California 94305 USA
- Yolanda Colino‐Sanguino
- Cancer Epigenetic Biology and Therapeutics Laboratory Children's Cancer Institute Randwick NSW 2052 Australia
- Laura Rodriguez de la Fuente
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Guocheng Fang
- Institute for Biomedical Materials and Devices (IBMD) Faculty of Science The University of Technology Sydney Ultimo NSW 2007 Australia
- Susan M. Grimes
- Division of Oncology Department of Medicine Stanford University California 94305 USA
- Hongxu Lu
- Institute for Biomedical Materials and Devices (IBMD) Faculty of Science The University of Technology Sydney Ultimo NSW 2007 Australia
- Robert J. Huang
- Division of Gastroenterology and Hepatology Department of Medicine Stanford University California 94305 USA
- Sarah T. Boyle
- Centre for Cancer Biology SA Pathology and University of South Australia Adelaide SA 5000 Australia
- Jeron Venhuizen
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Lesley Castillo
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Javad Tavakoli
- School of Biomedical Engineering Faculty of Engineering and Information Technology University of Technology Sydney NSW 2007 Australia
- Joanna N. Skhinas
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Ewan K. A. Millar
- Department of Anatomical Pathology NSW Health Pathology St George Hospital Kogarah NSW 2217 Australia
- Julia Beretov
- Department of Anatomical Pathology NSW Health Pathology St George Hospital Kogarah NSW 2217 Australia
- Fernando J. Rossello
- Centre for Cancer Research University of Melbourne Parkville VIC 3010 Australia
- Joanne L. Tipper
- School of Biomedical Engineering Faculty of Engineering and Information Technology University of Technology Sydney NSW 2007 Australia
- Christopher J. Ormandy
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Michael S. Samuel
- Centre for Cancer Biology SA Pathology and University of South Australia Adelaide SA 5000 Australia
- Thomas R. Cox
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- Luciano Martelotto
- Single Cell Core Systems Biology Harvard Medical School Harvard University Massachusetts 02115 USA
- Dayong Jin
- Institute for Biomedical Materials and Devices (IBMD) Faculty of Science The University of Technology Sydney Ultimo NSW 2007 Australia
- Fatima Valdes‐Mora
- Cancer Epigenetic Biology and Therapeutics Laboratory Children's Cancer Institute Randwick NSW 2052 Australia
- Hanlee P. Ji
- Division of Oncology Department of Medicine Stanford University California 94305 USA
- David Gallego‐Ortega
- The Kinghorn Cancer Centre Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia
- DOI
- https://doi.org/10.1002/advs.202103332
- Journal volume & issue
-
Vol. 9,
no. 21
pp. n/a – n/a
Abstract
Abstract 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.
Keywords
- alginate
- ex vivo drug screening
- single‐cell RNAseq
- three dimensional culture
- tissue microenvironment
- whole‐tissue organoids
