Modeling Metastatic Colonization in a Decellularized Organ Scaffold-Based Perfusion Bioreactor

Maria Rafaeva, Edward R Horton, Adina R D Jensen, Chris D Madsen, Raphael Reuten, Oliver Willacy, Christian B Brøchner, Thomas H Jensen, Kamilla Westarp Zornhagen, Marina Crespo, Dina S Grønseth, Sebastian R Nielsen, Manja Idorn, Per Thor Straten, Kristoffer Rohrberg, Iben Spanggaard, Martin Højgaard, Ulrik Lassen, Janine T Erler*, Alejandro E Mayorca-Guiliani*

*Corresponding author for this work
11 Citations (Scopus)

Abstract

Metastatic cancer spread is responsible for most cancer-related deaths. To colonize a new organ, invading cells adapt to, and remodel, the local extracellular matrix (ECM), a network of proteins and proteoglycans underpinning all tissues, and a critical regulator of homeostasis and disease. However, there is a major lack in tools to study cancer cell behavior within native 3D ECM. Here, an in-house designed bioreactor, where mouse organ ECM scaffolds are perfused and populated with cells that are challenged to colonize it, is presented. Using a specialized bioreactor chamber, it is possible to monitor cell behavior microscopically (e.g., proliferation, migration) within the organ scaffold. Cancer cells in this system recapitulate cell signaling observed in vivo and remodel complex native ECM. Moreover, the bioreactors are compatible with co-culturing cell types of different genetic origin comprising the normal and tumor microenvironment. This degree of experimental flexibility in an organ-specific and 3D context, opens new possibilities to study cell-cell and cell-ECM interplay and to model diseases in a controllable organ-specific system ex vivo.

Original languageEnglish
Article number2100684
JournalAdvanced healthcare materials
Volume11
Issue number1
ISSN2192-2640
DOIs
Publication statusPublished - 5 Jan 2022

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