Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids

Elisabeth Prince, Jennifer Cruickshank, Wail Ba-Alawi, Kelsey Hodgson, Jillian Haight, Chantal Tobin, Andrew Wakeman, Alona Avoulov, Valentina Topolskaia, Mitchell J. Elliott, Alison P. McGuigan, Hal K. Berman, Benjamin Haibe-Kains, David W. Cescon () and Eugenia Kumacheva ()
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Elisabeth Prince: University of Toronto
Jennifer Cruickshank: Princess Margaret Cancer Centre, University Health Network
Wail Ba-Alawi: Princess Margaret Cancer Centre, University Health Network
Kelsey Hodgson: Princess Margaret Cancer Centre, University Health Network
Jillian Haight: Princess Margaret Cancer Centre, University Health Network
Chantal Tobin: Princess Margaret Cancer Centre, University Health Network
Andrew Wakeman: Princess Margaret Cancer Centre, University Health Network
Alona Avoulov: University of Toronto
Valentina Topolskaia: University of Toronto
Mitchell J. Elliott: Princess Margaret Cancer Centre, University Health Network
Alison P. McGuigan: University of Toronto
Hal K. Berman: Princess Margaret Cancer Centre, University Health Network
Benjamin Haibe-Kains: Princess Margaret Cancer Centre, University Health Network
David W. Cescon: Princess Margaret Cancer Centre, University Health Network
Eugenia Kumacheva: University of Toronto

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Patient-derived tumor organoids (PDOs) are a highly promising preclinical model that recapitulates the histology, gene expression, and drug response of the donor patient tumor. Currently, PDO culture relies on basement-membrane extract (BME), which suffers from batch-to-batch variability, the presence of xenogeneic compounds and residual growth factors, and poor control of mechanical properties. Additionally, for the development of new organoid lines from patient-derived xenografts, contamination of murine host cells poses a problem. We propose a nanofibrillar hydrogel (EKGel) for the initiation and growth of breast cancer PDOs. PDOs grown in EKGel have histopathologic features, gene expression, and drug response that are similar to those of their parental tumors and PDOs in BME. In addition, EKGel offers reduced batch-to-batch variability, a range of mechanical properties, and suppressed contamination from murine cells. These results show that EKGel is an improved alternative to BME matrices for the initiation, growth, and maintenance of breast cancer PDOs.

Date: 2022
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DOI: 10.1038/s41467-022-28788-6

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