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

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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.

TidsskriftAdvanced Healthcare Materials
Udgave nummer1
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The authors thank I. Novak and N. Meyn Christensen (Centre for Advanced Bioimaging (CAB), University of Copenhagen) for providing microscope access. The authors would like to acknowledge Dr. Andrew Gerry and Dr. Bent Jakobsen of Adaptimmune Ltd. (Oxfordshire, UK) for supplying lentiviral vectors for high affinity MAGE‐A3a3a. The authors thank Svend‐Erik Lorentzen for providing technical support. This work was supported by the European Research Council (ERC‐2015‐CoG‐682881‐MATRICAN; R.R., A.E.M.‐G., and J.T.E.); a Ph.D. fellowship from the Lundbeck Foundation (R286‐2018‐621; M.R.); a Hallas Møller Stipend from the Novo Nordisk Foundation (J.T.E.); Innovation Fund Denmark Grand Solutions project (6153‐00015B; K.W.Z., M.C., K.R., I.S., M.H., U.L., and J.T.E.); the Danish Cancer Society (R204‐A12445; E.R.H.; R204‐A12454; R.R.); the Ragnar Söderberg Foundation (N91/15, C.D.M.), the Swedish cancer society, Cancerfonden (CAN 2016/783, C.D.M.; 19 0632 Pj, C.D.M.), the Swedish Research Council (2017‐03389, C.D.M.), and the German Cancer Aid (R.R.).

Publisher Copyright:
© 2021 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH

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