An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues

Nancy T Li; Nila C Wu; Ruonan Cao; Jose L Cadavid; Simon Latour; Xiaoya Lu; Yutong Zhu; Mirjana Mijalkovic; Reza Roozitalab; Natalie Landon-Brace; Faiyaz Notta; Alison P McGuigan

doi:10.1016/j.biomaterials.2022.121883

An off-the-shelf multi-well scaffold-supported platform for tumour organoid-based tissues

Biomaterials. 2022 Dec:291:121883. doi: 10.1016/j.biomaterials.2022.121883. Epub 2022 Oct 27.

Authors

Affiliations

¹ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.
² Institute of Biomedical Engineering, University of Toronto, Canada.
³ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada; Institute of Biomedical Engineering, University of Toronto, Canada.
⁴ Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK.
⁵ Princess Margaret Cancer Centre, University Health Network, Toronto, ON, M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 1L7, Canada; PanCuRx Translational Research Initiative, Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada.
⁶ Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada; Institute of Biomedical Engineering, University of Toronto, Canada. Electronic address: alison.mcguigan@utoronto.ca.

PMID: 36343611
DOI: 10.1016/j.biomaterials.2022.121883

Abstract

Complex 3D bioengineered tumour models provide the opportunity to better capture the heterogeneity of patient tumours. Patient-derived organoids are emerging as a useful tool to study tumour heterogeneity and variation in patient responses. Organoid cultures typically require a 3D microenvironment that can be manufactured easily to facilitate screening. Here we set out to create a high-throughput, "off-the-shelf" platform which permits the generation of organoid-containing engineered microtissues for standard phenotypic bioassays and image-based readings. To achieve this, we developed the Scaffold-supported Platform for Organoid-based Tissues (SPOT) platform. SPOT is a 3D gel-embedded in vitro platform that can be produced in a 96- or 384-well plate format and enables the generation of flat, thin, and dimensionally-defined microgels. SPOT has high potential for adoption due to its reproducible manufacturing methodology, compatibility with existing instrumentation, and reduced within-sample and between-sample variation, which can pose challenges to both data analysis and interpretation. Using SPOT, we generate cultures from patient derived pancreatic ductal adenocarcinoma organoids and assess the cellular response to standard-of-care chemotherapeutic compounds, demonstrating our platform's usability for drug screening. We envision 96/384-SPOT will provide a useful tool to assess drug sensitivity of patient-derived organoids and easily integrate into the drug discovery pipeline.

Keywords: 3D in vitro model; Drug response; High-throughput; Pancreatic Cancer; Paper based model; Patient-derived organoids; Tissue Engineering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Pancreatic Ductal* / pathology
Drug Discovery
Drug Evaluation, Preclinical / methods
Humans
Organoids / pathology
Pancreatic Neoplasms* / pathology
Tumor Microenvironment