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ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010 Australia.
Division of Oncology, Department of Medicine, Stanford University, California, 94305 USA.
Cancer Epigenetic Biology and Therapeutics Laboratory, Children's Cancer Institute, Randwick, NSW, 2052 Australia; School of Women's and Children's Health, Faculty of Medicine, University of New South Wales Sydney, NSW, 2052 Australia.
The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010 Australia; Cancer Epigenetic Biology and Therapeutics Laboratory, Children's Cancer Institute, Randwick, NSW, 2052 Australia.
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2022 (English)In: Advanced Science, E-ISSN 2198-3844, Vol. 9, no 21, article id 2103332Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022. Vol. 9, no 21, article id 2103332
Keywords [en]
alginate, ex vivo drug screening, single-cell RNAseq, three dimensionalculture, tissue microenvironment, whole-tissue organoids
National Category
Biophysics Bioinformatics and Systems Biology
Research subject
Machine Elements
Identifiers
URN: urn:nbn:se:ltu:diva-91234DOI: 10.1002/advs.202103332ISI: 000801181200001PubMedID: 35611998Scopus ID: 2-s2.0-85130552757OAI: oai:DiVA.org:ltu-91234DiVA, id: diva2:1673096
Note

Validerad;2022;Nivå 2;2022-08-04 (hanlid);

Funder: Cancer Council New South Wales (RG18-03); US National Institutes of Health (R01HG006137); National Breast Cancer Foundation (IIRS-21-096); Cancer Institute New South Wales (CDF181218); American Cancer Society (124571-RSG-13-297-01); Clayville Foundation; Gastric Cancer Foundation; NHMRC (GNT114519, GNT1184809, GNT2012941, GNT1158590)

Available from: 2022-06-20 Created: 2022-06-20 Last updated: 2022-10-21Bibliographically approved

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